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Sample records for overcome steric barriers

  1. Transforming Education: Overcoming Barriers.

    ERIC Educational Resources Information Center

    David, Jane L.; Goren, Paul D.

    Barriers to progress in educational reform exist inside and outside the education system. Some arise where new practices encounter traditional expectations and boundaries, but others go much deeper than education, such as poverty, racism, local political conflicts, and human resistance to change. The following five categories of barriers are…

  2. OVERCOMING CULTURAL BARRIERS.

    ERIC Educational Resources Information Center

    BARRUTIA, RICHARD

    THE RELATIONSHIP OF LANGUAGE DEVELOPMENT TO CULTURAL BARRIERS AND THE TEACHING OF FOREIGN LANGUAGES IS DISCUSSED IN THIS ARTICLE. VARIOUS VIEWS OF THE MEANING OF CULTURE ARE MENTIONED IN ORDER TO SINGLE OUT ANTHROPOLOGICAL CULTURE AS A MAIN FOCAL POINT. INTERCULTURAL DIFFERENCES ARE SPELLED OUT WITH EXAMPLES OF LINGUISTIC BARRIERS, AND…

  3. Overcoming Language Barriers

    PubMed Central

    De Buda, Yvonne

    1976-01-01

    Many family physicians in Canada experience language and cultural barriers between themselves and their patients. Several aspects of the ensuing problems are described and some practical suggestions for solutions are made. The importance of health education for new Canadians in the family physician's office as well as through the media and community projects is stressed. Imagesp68-ap68-bp70-a PMID:21308059

  4. Overcoming Barriers: Women in Superintendency

    ERIC Educational Resources Information Center

    Miller, Claire M.

    2009-01-01

    Women currently represent the largest number of teachers in the United States but remain underrepresented in the superintendent position. This suggests that the superintendency has been influenced by patriarchy. If women are to break through the barriers that prevent them from attaining a superintendency, we will need to understand the social…

  5. Overcoming Barriers: Women in Superintendency

    ERIC Educational Resources Information Center

    Miller, Claire M.

    2009-01-01

    Women currently represent the largest number of teachers in the United States but remain underrepresented in the superintendent position. This suggests that the superintendency has been influenced by patriarchy. If women are to break through the barriers that prevent them from attaining a superintendency, we will need to understand the social…

  6. Overcoming Barriers in Unhealthy Settings

    PubMed Central

    Lemke, Michael K.; Meissen, Gregory J.; Apostolopoulos, Yorghos

    2016-01-01

    We investigated the phenomenon of sustained health-supportive behaviors among long-haul commercial truck drivers, who belong to an occupational segment with extreme health disparities. With a focus on setting-level factors, this study sought to discover ways in which individuals exhibit resiliency while immersed in endemically obesogenic environments, as well as understand setting-level barriers to engaging in health-supportive behaviors. Using a transcendental phenomenological research design, 12 long-haul truck drivers who met screening criteria were selected using purposeful maximum sampling. Seven broad themes were identified: access to health resources, barriers to health behaviors, recommended alternative settings, constituents of health behavior, motivation for health behaviors, attitude toward health behaviors, and trucking culture. We suggest applying ecological theories of health behavior and settings approaches to improve driver health. We also propose the Integrative and Dynamic Healthy Commercial Driving (IDHCD) paradigm, grounded in complexity science, as a new theoretical framework for improving driver health outcomes. PMID:28462332

  7. Overcome barriers to career success

    SciTech Connect

    Raudsepp, E.

    1983-04-01

    A test is given to determine if an engineer suffers from one of the three barriers to technical success: fear of success, fear of failure, or perfectionism. As in most such tests, the middle way is best. Successful engineers know that perfection cannot be attained, that they don't have time to worry about failure or success, and that by aiming and perservering in doing things well, success can be achieved.

  8. Overcoming Barriers in the Media Center

    ERIC Educational Resources Information Center

    Winter, Clint

    2011-01-01

    Web 2.0 has revolutionized one's ability to teach students in new and exciting ways. Students with disabilities can now overcome many barriers that once kept them from being successful in the regular education classroom. Media specialists can effectively advocate for students with disabilities. School library media specialists have the ability to…

  9. Overcoming Barriers to Engaging in College Academics

    ERIC Educational Resources Information Center

    Hensley, Lauren; Shaulskiy, Stephanie; Zircher, Andrew; Sanders, Megan

    2015-01-01

    Underprepared college students face transition issues that prevent full academic engagement. The written responses of 176 students in a learning-strategies course were used to develop a grounded model of overcoming barriers to academic engagement. Findings revealed contexts in which academic engagement involved high costs (i.e., effort, trade-off,…

  10. Overcoming Barriers to Engaging in College Academics

    ERIC Educational Resources Information Center

    Hensley, Lauren; Shaulskiy, Stephanie; Zircher, Andrew; Sanders, Megan

    2015-01-01

    Underprepared college students face transition issues that prevent full academic engagement. The written responses of 176 students in a learning-strategies course were used to develop a grounded model of overcoming barriers to academic engagement. Findings revealed contexts in which academic engagement involved high costs (i.e., effort, trade-off,…

  11. Overcoming Barriers to Palliative Care Consultation.

    PubMed

    Perrin, Kathleen Ouimet; Kazanowski, Mary

    2015-10-01

    Palliative care consultations for patients with life-threatening illnesses provide benefits for the patients and their families as well as for the health care team. Patients have better quality of life and live longer but cost the health care system less. Still, many patients are not offered the opportunity to receive a palliative care consultation. Barriers to palliative care consultation for patients in critical care units include misunderstandings about palliative care and not having agreed upon criteria for referral. Critical care nurses can assist in overcoming these barriers.

  12. Weather in Mountainous Terrain (Overcoming Scientific Barriers to Weather Support)

    DTIC Science & Technology

    2011-02-15

    Weather in Mountainous Terrain (Overcoming Scientific Barriers to Weather Support) Fiesta Resort & Conference Center Tempe, AZ February 1...Meteorology Overcoming Scientific Barriers to Weather Support Fiesta Resort & Conference Center Tempe, AZ February 1 & 2, 2010 Hosted by University

  13. Overcoming pain as a barrier to work.

    PubMed

    Wynne-Jones, Gwenllian; Main, Chris J

    2011-06-01

    To consider whether pain is a barrier to work and if so how this can be overcome. Recent findings demonstrate that in addition to absence, pain can lead to a significant loss of productivity. The reasons why employees take absence or attend work while ill are complex and include personal, social and moral pressures around absence, and personally and institutionally mediated presenteeism. Interventions have moved on from a purely biomedical or psychosocial focus towards integrated programmes supporting individuals in managing their pain in the workplace. Pain is one of the leading causes of absenteeism and presenteeism with related costs for both employees and employers. Ongoing pain presents a number of physical, psychological and social obstacles to work, which may or may not be modifiable. A range of interventions has been tested in randomized trials with a recent move towards identifying and tackling musculoskeletal pain in the wider context as conceptualized by the flags framework. However, in order for any intervention to be successful in ensuring employees overcome pain as a barrier to work, there needs to be widespread change in behaviour with regard to occupational health in general and effective interventions need to be implemented in both workplace and healthcare settings.

  14. Fortification: overcoming technical and practical barriers.

    PubMed

    Hurrell, Richard F

    2002-04-01

    The main barriers to successful iron fortification are the following: 1) finding an iron compound that is adequately absorbed but causes no sensory changes to the food vehicle; and 2) overcoming the inhibitory effect on iron absorption of dietary components such as phytic acid, phenolic compounds and calcium. These barriers have been successfully overcome with some food vehicles but not with others. Iron-fortified fish sauce, soy sauce, curry powder, sugar, dried milk, infant formula and cereal based complementary foods have been demonstrated to improve iron status in targeted populations. The reasons for this success include the use of soluble iron such as ferrous sulfate, the addition of ascorbic acid as an absorption enhancer or the use of NaFeEDTA to overcome the negative effect of phytic acid. In contrast, at the present time, it is not possible to guarantee a similar successful fortification of cereal flours or salt. There is considerable doubt that the elemental iron powders currently used to fortify cereal flours are adequately absorbed, and there is an urgent need to investigate their potential for improving iron status. Better absorbed alternative compounds for cereal fortification include encapsulated ferrous sulfate and NaFeEDTA, which, unlike ferrous sulfate, do not provoke fat oxidation of cereals during storage. Encapsulated compounds also offer a possibility to fortify low grade salt without causing off-colors or iodine loss. Finally, a new and useful additional approach to ensuring adequate iron absorption from cereal based complementary foods is the complete degradation of phytic acid with added phytases or by activating native cereal phytases.

  15. Steric, Quantum, and Electrostatic Effects on SN2 Reaction Barriers in Gas Phase

    SciTech Connect

    Liu, Shubin; Hu, Hao; Pedersen, Lee G.

    2010-05-13

    Biomolecular nucleophilic substitution reactions, S{sub N}2, are fundamental and commonplace in chemistry. It is the well-documented experimental finding in the literature that vicinal substitution with bulkier groups near the reaction center significantly slows the reaction due to steric hindrance, but theoretical understanding in the quantitative manner about factors dictating the S{sub N}2 reaction barrier height is still controversial. In this work, employing the new quantification approach that we recently proposed for the steric effect from the density functional theory framework, we investigate the relative contribution of three independent effects—steric, electrostatic, and quantum—to the S{sub N}2 barrier heights in gas phase for substituted methyl halide systems, R{sub 1}R{sub 2}R{sub 3}CX, reacting with the fluorine anion, where R{sub 1}, R{sub 2}, and R{sub 3} denote substituting groups and X = F or Cl. We found that in accordance with the experimental finding, for these systems, the steric effect dominates the transition state barrier, contributing positively to barrier heights, but this contribution is largely compensated by the negative, stabilizing contribution from the quantum effect due to the exchange-correlation interactions. Moreover, we find that it is the component from the electrostatic effect that is linearly correlated with the S{sub N}2 barrier height for the systems investigated in the present study. In addition, we compared our approach with the conventional method of energy decomposition in density functional theory as well as examined the steric effect from the wave function theory for these systems via natural bond orbital analysis.

  16. Overcoming a nucleosomal barrier to replication

    PubMed Central

    Chang, Han-Wen; Pandey, Manjula; Kulaeva, Olga I.; Patel, Smita S.; Studitsky, Vasily M.

    2016-01-01

    Efficient overcoming and accurate maintenance of chromatin structure and associated histone marks during DNA replication are essential for normal functioning of the daughter cells. However, the molecular mechanisms of replication through chromatin are unknown. We have studied traversal of uniquely positioned mononucleosomes by T7 replisome in vitro. Nucleosomes present a strong, sequence-dependent barrier for replication, with particularly strong pausing of DNA polymerase at the +(31–40) and +(41–65) regions of the nucleosomal DNA. The exonuclease activity of T7 DNA polymerase increases the overall rate of progression of the replisome through a nucleosome, likely by resolving nonproductive complexes. The presence of nucleosome-free DNA upstream of the replication fork facilitates the progression of DNA polymerase through the nucleosome. After replication, at least 50% of the nucleosomes assume an alternative conformation, maintaining their original positions on the DNA. Our data suggest a previously unpublished mechanism for nucleosome maintenance during replication, likely involving transient formation of an intranucleosomal DNA loop. PMID:27847876

  17. Fisher information and steric effect: study of the internal rotation barrier of ethane.

    PubMed

    Esquivel, Rodolfo O; Liu, Shubin; Angulo, Juan Carlos; Dehesa, Jesús S; Antolín, Juan; Molina-Espíritu, Moyocoyani

    2011-05-05

    On the basis of a density-based quantification of the steric effect [Liu, S. B. J. Chem. Phys.2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane is systematically investigated in this work from an information-theoretical point of view by using the Fisher information measure in conjugated spaces. Two kinds of computational approaches are considered in this work: adiabatic (with optimal structure) and vertical (with fixed geometry). The analyses are performed systematically by following, in each case, the conformeric path by changing the dihedral angle from 0 to 180° . This is calculated at the HF, MP2, B3LYP, and CCSD(T) levels of theory and with several basis sets. Selected descriptors of the densities are utilized to support the observations. Our results show that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer, but in the vertical cases the staggered conformer retains a larger steric repulsion. Our results verify the plausibility for defining and computing the steric effect in the post-Hartree-Fock level of theory according to the scheme proposed by Liu.

  18. Consumer and Employer Strategies for Overcoming Employment Barriers. Technical Report.

    ERIC Educational Resources Information Center

    Crudden, Adele; Williams, Wendy; McBroom, Lynn W.; Moore, J. Elton

    This report on strategies for overcoming employment barriers for persons with visual impairments summarizes comments and suggestions of 7 focus groups comprised of either consumers (n=49) or employers (n=19). The report first reviews the literature concerning employment barriers and how consumers in previous studies suggested these barriers be…

  19. Overcoming Blocks and Barriers to Creativity.

    ERIC Educational Resources Information Center

    Raudsepp, Eugene

    1982-01-01

    Organizational barriers to creativity are examined. It is noted that resistance to change is a major impediment to creative problem solving in most organizations. Understanding the barriers to change that exist is viewed to help people exercise and develop their creativity more fully and effectively. (MP)

  20. Overcoming Blocks and Barriers to Creativity.

    ERIC Educational Resources Information Center

    Raudsepp, Eugene

    1982-01-01

    Organizational barriers to creativity are examined. It is noted that resistance to change is a major impediment to creative problem solving in most organizations. Understanding the barriers to change that exist is viewed to help people exercise and develop their creativity more fully and effectively. (MP)

  1. Explaining and overcoming barriers to climate change adaptation

    NASA Astrophysics Data System (ADS)

    Eisenack, Klaus; Moser, Susanne C.; Hoffmann, Esther; Klein, Richard J. T.; Oberlack, Christoph; Pechan, Anna; Rotter, Maja; Termeer, Catrien J. A. M.

    2014-10-01

    The concept of barriers is increasingly used to describe the obstacles that hinder the planning and implementation of climate change adaptation. The growing literature on barriers to adaptation reveals not only commonly reported barriers, but also conflicting evidence, and few explanations of why barriers exist and change. There is thus a need for research that focuses on the interdependencies between barriers and considers the dynamic ways in which barriers develop and persist. Such research, which would be actor-centred and comparative, would help to explain barriers to adaptation and provide insights into how to overcome them.

  2. Overcoming Blocks and Barriers to Creativity.

    ERIC Educational Resources Information Center

    Raudsepp, Eugene

    1982-01-01

    The most serious blocks to creative thinking are viewed as psychological in nature. These obstacles are the hardest to recognize and overcoming them requires changing basic personality traits that have been years in the making. Tips on how individuals can gather self-knowledge and express individuality and creativity are given. (MP)

  3. Overcoming cellular barriers for RNA therapeutics.

    PubMed

    Dowdy, Steven F

    2017-03-01

    RNA-based therapeutics, such as small-interfering (siRNAs), microRNAs (miRNAs), antisense oligonucleotides (ASOs), aptamers, synthetic mRNAs and CRISPR-Cas9, have great potential to target a large part of the currently undruggable genes and gene products and to generate entirely new therapeutic paradigms in disease, ranging from cancer to pandemic influenza to Alzheimer's disease. However, for these RNA modalities to reach their full potential, they first need to overcome a billion years of evolutionary defenses that have kept RNAs on the outside of cells from invading the inside of cells. Overcoming the lipid bilayer to deliver RNA into cells has remained the major problem to solve for widespread development of RNA therapeutics, but recent chemistry advances have begun to penetrate this evolutionary armor.

  4. Overcoming the English-language barrier

    NASA Astrophysics Data System (ADS)

    Mahoney, Terry J.

    Astronomers from non-English-speaking countries, who form a sizeable proportion of the astronomical research community, are obliged to communicate the results of their investigations in a language that is not their own. Consequently, good science is frequently masked by poor command of English, which can create an unnecessary barrier to the communication of scientific results. A suggested method of surmounting the language barrier is the setting up of scientific editorial services in at least the major astronomical centres. It is further argued that journal editors, rather than scientific referees, should be responsible for judging the linguistic and stylistic quality of articles presented for publication. The peer-review system would then be restricted exclusively to the scientific rather than linguistic content of papers presented. The scientific Editorial Service of the Instituto de Astrofisica de Canarias, in operation since 1996, is briefly described in this context.

  5. Dos Hermanas Chicanas: Overcoming Barriers to Professional Advancement

    ERIC Educational Resources Information Center

    Prospero, Moises

    2007-01-01

    Women and ethnic minorities face steep barriers to professional advancement, and those who rise to the executive level typically use a variety of strategies to overcome obstacles in their way. This study first reviewed the literature on barriers to professional advancement for women and ethnic minorities and the strategies that they report using…

  6. Overcoming learning barriers through knowledge management.

    PubMed

    Dror, Itiel E; Makany, Tamas; Kemp, Jonathan

    2011-02-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and financial sector. We examined comprehension, accuracy, mental imagery & complexity, metacognition, and memory. We found that participants with dyslexia, when using a non-linear note-taking technique outperformed the control group using linear note-taking and matched the performance of the control group using non-linear note-taking. These findings emphasize how different knowledge management techniques can avoid some of the barriers to learners.

  7. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    PubMed Central

    Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

    2017-01-01

    HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

  8. Steric and interactive barrier properties of intestinal mucus elucidated by particle diffusion and peptide permeation.

    PubMed

    Boegh, Marie; García-Díaz, María; Müllertz, Anette; Nielsen, Hanne Mørck

    2015-09-01

    The mucus lining of the gastrointestinal tract epithelium is recognized as a barrier to efficient oral drug delivery. Recently, a new in vitro model for assessment of drug permeation across intestinal mucosa was established by applying a biosimilar mucus matrix to the surface of Caco-2 cell monolayers. The aim of the present study was to gain more insight into the steric and interactive barrier properties of intestinal mucus by studying the permeation of peptides and model compounds across the biosimilar mucus as well as across porcine intestinal mucus (PIM). As PIM disrupted the Caco-2 cell monolayers, a cell-free mucus barrier model was implemented in the studies. Both the biosimilar mucus and the PIM reduced the permeation of the selected peptide drugs to varying degrees illustrating the interactive properties of both mucus matrices. The reduction in peptide permeation was decreased depending on the cationicity and H-bonding capacity of the permeant clearly demonstrated by using the biosimilar mucus, whereas the larger inter sample variation of the PIM matrix obstructed similarly clear conclusions. Thus, for mechanistic studies of permeation across mucus and mucosa the biosimilar mucus offers a relevant and reproducible alternative to native mucus. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

    PubMed Central

    Jones, Charles H.; Chen, Chih-Kaung; Ravikrishnan, Anitha; Rane, Snehal; Pfeifer, Blaine A.

    2013-01-01

    A key end goal of gene delivery research is to develop clinically-relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in sub-viral performance. In this perspective, we concentrate on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers. We present the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers. PMID:24093932

  10. Overcoming Barriers to School Based Research: A Local School Perspective.

    ERIC Educational Resources Information Center

    Epps, Jean M.

    The importance of collaboration between professional research and professional personnel in the classroom and school office is described, and suggestions are made for overcoming barriers to effective collaboration. Crandall's conditions for effective collaboration are: that the participants possess substantive competency; that both organizations…

  11. Overcoming Barriers to School Based Research: A Local School Perspective.

    ERIC Educational Resources Information Center

    Epps, Jean M.

    The importance of collaboration between professional research and professional personnel in the classroom and school office is described, and suggestions are made for overcoming barriers to effective collaboration. Crandall's conditions for effective collaboration are: that the participants possess substantive competency; that both organizations…

  12. Overcoming barriers to Baby-Friendly status: one hospital's experience.

    PubMed

    McKeever, Joyce; Fleur, Rose St

    2012-08-01

    The journey toward Baby-Friendly status at Jersey Shore University Medical Center in Neptune, NJ began with a desire to improve overall breastfeeding rates at the hospital. Although evidence showed that hospitals that incorporated some or all of the Ten Steps to Successful Breastfeeding had improved breastfeeding rates, it was difficult to overcome barriers that prevented the hospital physicians and nursing staff from seeing the value in adopting this quality initiative. Long-standing practices combined with misinformation compounded the problem. That situation changed when several factors nationally and statewide came together to create a prime environment for implementation of the Baby-Friendly Hospital Initiative. This article will discuss the barriers that one hospital encountered and the strategies used to overcome these common barriers to achieving Baby-Friendly status. This hospital is not yet designated as Baby-Friendly but is awaiting the outcome of a site visit in 2012.

  13. Overcoming of energy barrier for irreversible magnetization in nanocomposite magnets

    NASA Astrophysics Data System (ADS)

    Li, Zhu-bai; Zhang, Ying; Shen, Bao-gen; Zhang, Ming; Hu, Feng-xia; Sun, Ji-rong

    2017-01-01

    The irreversible magnetization occurs mainly in hard grains in nanocomposite magnets, and the domain wall involves a little part of defect region in irreversible magnetization due to the self-interaction. The investigation on thermal activation shows that the defect region involved in domain wall becomes narrower due to the TiNb addition in Pr2Fe14B/α-Fe magnets. The defect region augments the energy density in the negative direction of domain wall to overcome the energy barrier of perfect hard region. The soft phase, exchange-coupled with defect region at hard grain outer-layer, promotes magnetization reversal in defect region by exchange coupling. While the defect region plays a role as a ladder to overcome the energy barrier, resulting in the decrease of coecivity more or less depending upon the width and anisotropy of defect region.

  14. Global Health and Emergency Care: Overcoming Clinical Research Barriers.

    PubMed

    Levine, Adam C; Barry, Meagan A; Agrawal, Pooja; Duber, Herbert C; Chang, Mary P; Mackey, Joy M; Hansoti, Bhakti

    2017-04-01

    There are many barriers impeding the conduct of high-quality emergency care research, particularly in low- and middle-income countries. Several of these barriers were originally outlined in 2013 as part of the Academic Emergency Medicine Global Health and Emergency Care Consensus Conference. This paper seeks to establish a broader consensus on the barriers to emergency care research globally and proposes a comprehensive array of new recommendations to overcome these barriers. An electronic survey was conducted of a purposive sample of global emergency medicine research experts from around the world to describe the major challenges and solutions to conducting emergency care research in low-resource settings and rank them by importance. The Global Emergency Medicine Think Tank Clinical Research Working Group at the Society for Academic Emergency Medicine 2016 Annual Meeting utilized a modified Delphi technique for consensus-based decision making to categorize and expand upon these barriers and develop a comprehensive array of proposed solutions. The working group identified four broad categories of barriers to conducting emergency care research globally, including 1) the limited availability of research personnel, particularly those with prior research training; 2) logistic barriers and lack of standardization of data collection; 3) ethical barriers to conducting research in resource-limited settings, particularly when no local institutional review board is available; and 4) the relative dearth of funding for global emergency care research. Proposed solutions included building a diverse and interdisciplinary research team structured to promote mentorship of junior researchers, utilizing local research assistants or technologic tools such as telemedicine for language translation, making use of new tools such as mobile health (mHealth) to standardize and streamline data collection, identifying alternatives to local institutional review board approval and the use of

  15. Overcoming barriers to health service access: influencing the demand side.

    PubMed

    Ensor, Tim; Cooper, Stephanie

    2004-03-01

    Evidence suggests that demand-side barriers may be as important as supply factors in deterring patients from obtaining treatment. Yet relatively little attention is given, either by policy makers or researchers, to ways of minimizing their effect. These barriers are likely to be more important for the poor and other vulnerable groups, where the costs of access, lack of information and cultural barriers impede them from benefiting from public spending. Demand barriers present in low- and middle-income countries and evidence on the effectiveness of interventions to overcome these obstacles are reviewed. Demand barriers are also shown to be important in richer countries, particularly among vulnerable groups. This suggests that while barriers are plentiful, there is a dearth of evidence on ways to reduce them. Where evidence does exist, the data and methodology for evaluating effectiveness and cost-effectiveness is insufficient. An increased focus on obtaining robust evidence on effective interventions could yield high returns. The likely nature of the interventions means that pragmatic policy routes that go beyond the traditional boundaries of the public health sector are required for implementing the findings.

  16. Overcoming translational barriers impeding development of Alzheimer's disease modifying therapies.

    PubMed

    Golde, Todd E

    2016-10-01

    It has now been ~ 30 years since the Alzheimer's disease (AD) research entered what may be termed the 'molecular era' that began with the identification of the amyloid β protein (Aβ) as the primary component of amyloid within senile plaques and cerebrovascular amyloid and the microtubule-associated protein tau as the primary component of neurofibrillary tangles in the AD brain. These pivotal discoveries and the subsequent genetic, pathological, and modeling studies supporting pivotal roles for tau and Aβ aggregation and accumulation have provided firm rationale for a new generation of AD therapies designed not to just provide symptomatic benefit, but as disease modifying agents that would slow or even reverse the disease course. Indeed, over the last 20 years numerous therapeutic strategies for disease modification have emerged, been preclinically validated, and advanced through various stages of clinical testing. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome barriers that are not major foci of current research efforts. Seminal discoveries made over the past 25 years have provided firm rationale for a new generation of Alzheimer's disease (AD) therapies designed as disease modifying agents that would slow or even reverse the disease course. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful AD disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome these barriers. This article is part of the 60th Anniversary special issue.

  17. Overcoming barriers to reducing the burden of affective disorders.

    PubMed

    Wells, Kenneth B; Miranda, Jeanne; Bauer, Mark S; Bruce, Martha L; Durham, Mary; Escobar, Javier; Ford, Daniel; Gonzalez, Junius; Hoagwood, Kimberly; Horwitz, Sarah M; Lawson, William; Lewis, Lydia; McGuire, Thomas; Pincus, Harold; Scheffler, Richard; Smith, William A; Unützer, Jürgen

    2002-09-15

    Affective disorders impose a substantial individual and societal burden. Despite availability of efficacious treatments and practice guidelines, unmet need remains high. To reduce unmet need and the burden of affective disorders, information is needed on the distribution of burden across stakeholders, on barriers to reducing burden, and on interventions that effectively reduce burden at the levels of practice, community, and policy. This article provides the report of the Working Group on Overcoming Barriers to Reducing the Burden of Affective Disorders, for the National Institute of Mental Health Strategic Plan on Mood Disorders. We review the literature, identify key gaps, and recommend new research to guide national efforts to reduce the burden of affective disorders.

  18. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier

    PubMed Central

    Hersh, David S.; Wadajkar, Aniket S.; Roberts, Nathan B.; Perez, Jimena G.; Connolly, Nina P.; Frenkel, Victor; Winkles, Jeffrey A.; Woodworth, Graeme F.; Kim, Anthony J.

    2016-01-01

    The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

  19. Overcoming barriers to pain relief in the Caribbean.

    PubMed

    Macpherson, Cheryl; Aarons, Derrick

    2009-12-01

    This paper examines pain and pain relief in the Caribbean, where pain is widely perceived as an unavoidable part of life, and where unnecessary suffering results from untreated and under treated pain. Barriers to pain relief in the Caribbean include patient and family attitudes, inadequate knowledge among health professionals and unduly restrictive regulations on the medical use of opioids. Similar barriers exist all over the world. This paper urges medical, nursing and public health professionals, and educators to examine attitudes towards pain and pain relief and to work towards making effective pain relief and palliation more accessible. It recommends that i) health professionals and officials be better educated about pain, palliation and opioids, ii) regulatory restrictions be updated in light of clinical and scientific evidence, iii) opioid procurement policies be adjusted to facilitate increased medical use, iv) medical charts and records be modified to routinely elicit and document patients levels of pain, and v) educational campaigns be developed to inform the public that moderate and severe pain can be safely relieved at the end of life and other stages of life. The professional, respectful, and beneficent response to patients in pain is to provide rapid and aggressive pain relief or to urgently consult a pain or palliative specialist. When a health system hinders such efforts the ethical response is to identify, facilitate and advocate for overcoming barriers to improvement.

  20. Barriers to women engaging in collective action to overcome sexism.

    PubMed

    Radke, Helena R M; Hornsey, Matthew J; Barlow, Fiona Kate

    2016-12-01

    Over centuries women have fought hard to obtain increasing gender equality, but despite these successes absolute equality remains an elusive goal. Theoretically, women's numerical strength makes them well-placed to take effective collective action, and millions of women engage in feminist collective action every day. In this article, however, we argue that women also face barriers to engaging in feminist collective action; barriers that are associated with the social construction and experience of what it means to be a woman. Our review synthesizes sexism research under a contemporary collective action framework to clarify our current understanding of the literature and to offer novel theoretical explanations for why women might be discouraged from engaging in feminist collective action. Using the antecedents of collective action identified by van Zomeren, Postmes, and Spears' (2008) meta-analysis, we critically review the sexism literature to argue that women face challenges when it comes to (a) identifying with other women and feminists, (b) perceiving sexism and expressing group-based anger, and (c) recognizing the efficacy of collective action. We then outline a research agenda with a view to investigating ways of overcoming these barriers. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Rotational barriers of biphenyls having heavy heteroatoms as ortho-substituents: experimental and theoretical determination of steric effects.

    PubMed

    Lunazzi, Lodovico; Mancinelli, Michele; Mazzanti, Andrea; Lepri, Susan; Ruzziconi, Renzo; Schlosser, Manfred

    2012-03-07

    The free energies of activation for the aryl-aryl rotation of 17 biphenyl derivatives, bearing a heavy heteroatom (S, Se, Te, P, Si, Sn) as ortho substituent, have been measured by variable temperature NMR. These numbers, so called B values, represent a meaningful measure of the steric hindrance exerted by the selected substituents. DFT computations match quite satisfactorily the experimental barriers and the ground state geometries as well (determined, in two cases, by X-ray diffraction). The present values extend the available list of B values and thus provide an enlarged basis for the compilation of the space requirements of standard substituents, based solely on experimental determinations.

  2. Self-induced dust traps: overcoming planet formation barriers

    NASA Astrophysics Data System (ADS)

    Gonzalez, J.-F.; Laibe, G.; Maddison, S. T.

    2017-01-01

    Planet formation is thought to occur in discs around young stars by the aggregation of small dust grains into much larger objects. The growth from grains to pebbles and from planetesimals to planets is now fairly well understood. The intermediate stage has however been found to be hindered by the radial-drift and fragmentation barriers. We identify a powerful mechanism in which dust overcomes both barriers. Its key ingredients are i) backreaction from the dust onto the gas, ii) grain growth and fragmentation, and iii) large-scale gradients. The pile-up of growing and fragmenting grains modifies the gas structure on large scales and triggers the formation of pressure maxima, in which particles are trapped. We show that these self-induced dust traps are robust: they develop for a wide range of disc structures, fragmentation thresholds and initial dust-to-gas ratios. They are favored locations for pebbles to grow into planetesimals, thus opening new paths towards the formation of planets.

  3. Challenges confronting female surgical leaders: overcoming the barriers.

    PubMed

    Kass, Rena B; Souba, Wiley W; Thorndyke, Luanne E

    2006-05-15

    The number of women reaching top ranks in academic surgery is remarkably low. The purpose of this study was to identify: 1) barriers to becoming a female surgical leader; 2) key attributes that enable advancement and success; and 3) current leadership challenges faced as senior leaders. Semi-structured interviews of ten female surgical leaders queried the following dimensions: attributes for success, lessons learned, mistakes, key career steps, the role of mentoring, gender advantages/disadvantages, and challenges. Perseverance (60%) and drive (50%) were identified as critical success factors, as were good communication skills, a passion for scholarship, a stable home life and a positive outlook. Eighty percent identified discrimination or gender prejudice as a major obstacle in their careers. While 90% percent had mentors, 50% acknowledged that they had not been effectively mentored. Career advice included: develop broad career goals (50%); select a conducive environment (30%); find a mentor (60%); take personal responsibility (40%); organize time and achieve balance (40%); network (30%); create a niche (30%); pursue research (30%); publish (50%); speak in public (30%); and enjoy the process (30%). Being in a minority, being highly visible and being collaborative were identified as advantages. Obtaining buy-in and achieving consensus was the greatest leadership challenge reported. Female academic surgeons face challenges to career advancement. While these barriers are real, they can be overcome by resolve, commitment, and developing strong communication skills. These elements should be taken into consideration in designing career development programs for junior female surgical faculty.

  4. Jumping Hurdles: Peptides Able To Overcome Biological Barriers.

    PubMed

    Sánchez-Navarro, Macarena; Teixidó, Meritxell; Giralt, Ernest

    2017-08-15

    diketoperazines (DKPs), (N-MePhe)n, or (PhPro)n. On the other hand, we have investigated BBB-shuttles that utilize active transport mechanisms such as SGV, THRre, or MiniAp-4. For the development of both groups, we have explored several approaches, such as the use of peptide libraries, both chemical and phage display, or hit-to-lead optimization processes. In this Account, we describe, in chronologic order, our contribution to the development of peptides able to overcome various biological barriers and our efforts to understand the mechanisms that they display. In addition, the potential use of both CPPs and BBB-shuttles to improve the transport of promising therapeutic compounds is described.

  5. Polymeric nanoparticles of different sizes overcome the cell membrane barrier.

    PubMed

    Lerch, Simone; Dass, Martin; Musyanovych, Anna; Landfester, Katharina; Mailänder, Volker

    2013-06-01

    Polymeric nanoparticles have tremendous potential either as carriers or markers in treatment for diseases or as diagnostics in biomedical applications. Finding the optimal conditions for effective intracellular delivery of the payload to the location of interest is still a big challenge. The particles have to overcome the barrier of the cell membrane. Here, we investigated the uptake in HeLa cells of fluorescent polystyrene particles with different size and surface charge. Particles stabilized with the nonionic surfactant Lutensol AT50® (132 nm, 180 nm, 242 nm, 816 nm, 846 nm diameter) were synthesized via dispersion polymerization. Cationic particles (120 nm, 208 nm, 267 nm, 603 nm diameter) were obtained by a combination of miniemulsion and seed dispersion polymerization using cationic surfactant (cetyltrimethylammonium chloride (CTMA-Cl). The particle uptake into HeLa cells was studied by confocal laser scanning microscopy and flow cytometry. Nonionic particles were - independent of their size - taken up by cells only at a barely detectable level, thus aggravating a quantitative comparison. The uptake of positively charged particles was substantially higher and therefore enabling further investigation keeping constant one of these parameters: either material amount or particles number or total interaction surface area. It was found that the uptake rather depends on the total amount of polymeric material present in the media than on the number of particles. The total particle's surface area does not correlate linearly with the uptake, thus indicating that there is no direct dependency between the total surface area and the cellular endocytotic process to overcome the biobarrier "cell membrane." A potentially novel uptake mechanism is found which can be described as an excavator shovel like mechanism. It is a kind of macropinocytosis dependent on actin filaments as well as dynamin, but is clathrin-independent.

  6. Overcoming barriers to integrating economic analysis into risk assessment.

    PubMed

    Hoffmann, Sandra

    2011-09-01

    Regulatory risk analysis is designed to provide decisionmakers with a clearer understanding of how policies are likely to affect risk. The systems that produce risk are biological, physical, and social and economic. As a result, risk analysis is an inherently interdisciplinary task. Yet in practice, risk analysis has been interdisciplinary in only limited ways. Risk analysis could provide more accurate assessments of risk if there were better integration of economics and other social sciences into risk assessment itself. This essay examines how discussions about risk analysis policy have influenced the roles of various disciplines in risk analysis. It explores ways in which integrated bio/physical-economic modeling could contribute to more accurate assessments of risk. It reviews examples of the kind of integrated economics-bio/physical modeling that could be used to enhance risk assessment. The essay ends with a discussion of institutional barriers to greater integration of economic modeling into risk assessment and provides suggestions on how these might be overcome.

  7. Immunotherapy and complexity: overcoming barriers to control of advanced cancer.

    PubMed

    Lage, Agustin

    2014-01-01

    Recent advances in fundamental immunology are changing paradigms for management of advanced cancer, now acknowledged as a chronic disease whose prevalence will increase, and one whose complexity makes it difficult to control. Immunotherapy is emerging as an alternative, with new monoclonal antibodies, therapeutic vaccines and deeper understanding of fundamental phenomena in the interaction between tumor and immune system. These novel insights concern mechanisms of programmed contraction of the immune response, characterization of molecular and cellular markers of immunosenescence, the dual role of inflammation, characterization of myeloid-derived suppressor cells and cancer stem cells, and the phenomena of immunogenic apoptosis and oncogene addiction. Additionally, new data drive a deeper understanding of four barriers to overcome in control of advanced cancer: the complexity of biological systems, tumor heterogeneity, tumor mutation rates, and human genome-environment mismatch. The new landscape points to six main strategies: manage advanced cancer as a chronic disease, find relevant molecular markers for patient stratification, develop a rationale for therapeutic combinations, target regulatory control loops in the immune system, expand mathematical modeling capacity, and evaluate complex health intervention packages in real-world conditions. These transitions in cancer immunotherapy research are illustrated in this paper through description of ongoing projects at Cuba's Molecular Immunology Center.

  8. 75 FR 58347 - Information Collection; Overcoming Barriers to Wildland Fire Defensible Space Behaviors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Information Collection; Overcoming Barriers to Wildland Fire... Fire Defensible Space Behaviors. DATES: Comments must be received in writing on or before November 23...: Overcoming Barriers to Wildland Fire Defensible Space Behaviors. OMB Number: 0596-New. Type of Request:...

  9. Identifying and Overcoming Barriers to Diabetes Management in the Elderly: An Intervention Study

    DTIC Science & Technology

    2010-06-01

    TITLE: Identifying and overcoming barriers to diabetes management in the elderly: an intervention study PRINCIPAL INVESTIGATOR: Dr. Medha Munshi...M.D. CONTRACTING ORGANIZATION: Joslin Diabetes Center, Inc...TITLE AND SUBTITLE Identifying and overcoming barriers to diabetes management in the elderly: 5a. CONTRACT NUMBER W81XWH-07-1-0282 An Intervention

  10. Overcoming Barriers to Wind Development in Appalachian Coal Country

    SciTech Connect

    Brent Bailey; Evan Hansen

    2012-10-09

    This research project synthesizes existing data and communication from experts to assess barriers to wind development in Pennsylvania, Maryland, West Virginia, Virginia, and Kentucky, and makes recommendations where feasible to reduce or eliminate those barriers.

  11. Psychology of Success: Overcoming Barriers to Pursuing Further Education

    ERIC Educational Resources Information Center

    Goto, Stanford T.; Martin, Connie

    2009-01-01

    Of the many barriers that prevent adults from continuing their education, psychological barriers are least often addressed by educators. This is an important area of concern because psychological factors influence how prospective students respond to other barriers. This qualitative study was conducted to describe how adults negotiate…

  12. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    EPA Science Inventory

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  13. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    EPA Science Inventory

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  14. Overcoming barriers to cancer pain management: an institutional change model.

    PubMed

    Sun, Virginia Chih-Yi; Borneman, Tami; Ferrell, Betty; Piper, Barbara; Koczywas, Marianna; Choi, Kyong

    2007-10-01

    The Agency for Health Care Policy and Research Pain Guidelines of 1994 recognized pain as a critical symptom that impacts quality of life (QOL). The barriers to optimum pain relief were classified into three categories: patient, professional, and system barriers. A prospective, longitudinal clinical trial is underway to test the effects of the "Passport to Comfort" innovative intervention on pain and fatigue management. This article reports on preintervention findings related to barriers to pain management. Cancer patients with a diagnosis of breast, lung, colon, or prostate cancer who reported a pain rating of >/=4 were accrued. Subjects completed questionnaires to assess subjective ratings of overall QOL, barriers to pain management, and pain knowledge at baseline and at one- and three-month evaluations. A chart audit was conducted at one month to document objective data related to pain management. The majority of subjects had moderate (4-6 on a 0-10 numeric rating scale) pain at the time of accrual. Patient barriers to pain management existed in attitudes and knowledge regarding addiction, tolerance, and not being able to control pain. Subjects who were currently receiving chemotherapy were reluctant to communicate their pain with health care professionals. Professional and system barriers were focused around screening, documentation, reassessment, and follow-up of pain. Lack of referrals to supportive care services for patients was also noted. Several well-described patient, professional, and system barriers continue to hinder efforts to provide optimal pain relief. Phase II of this initiative will attempt to eliminate these barriers using the "Passport" intervention to manage cancer pain.

  15. Concept-Based Curriculum: Changing Attitudes and Overcoming Barriers.

    PubMed

    Hendricks, Susan M; Wangerin, Virginia

    Many nursing educators have considered the implementation of a concept-based curriculum, with active, conceptual teaching and learning strategies, which offers a way to respond to the overwhelming content saturation in many nursing curricula. However, barriers abound, including faculty concerns about loss of control, changing faculty role and identity, and fear of failure. This article clarifies these legitimate barriers and offers practical strategies for success in curriculum change.

  16. Overcoming Institutional Barriers to Broad-Based Curricular Change.

    ERIC Educational Resources Information Center

    Elliott, Donald; And Others

    1993-01-01

    The recent experience of the business school at Southern Illinois University at Edwardsville in overcoming structural obstacles to curriculum development is discussed. Drawing on an automobile industry model for organizational change, the school used an interdisciplinary approach to curriculum design and implementation. Characteristics of the…

  17. Overcoming the ten most common barriers to effective team communication.

    PubMed

    Hills, Laura

    2013-01-01

    Communication is at the heart of medical practice management. Yet there are many barriers to effective communication that can interfere with the smooth running of the practice. This article describes the 10 most common barriers to effective medical practice team communication and offers six steps the practice manager can take to break them down. This article also suggests that the practice develop a team communication strategy. It suggests 10 communication principles readers can share directly with their teams and describes three hallmarks of effective team communication. Finally, this article provides a list of 25 practical questions practice managers can use to improve their team's communication.

  18. Retaining Talent for Army 2020: Overcoming Institutional Barriers

    DTIC Science & Technology

    2012-03-19

    dustbin of history, overcome by institutional bureaucratic pressures . The Army’s anticipated restructure (downsizing) of the All-Volunteer force...presents a challenge to ensure the retention of high potential junior officer talent in the Officer Corps for senior level positions for the Army of...2020. U.S. military leaders understand that we must balance the tension between winning the current fight with the high level of performance and

  19. Automation U.S.A.: Overcoming Barriers to Automation.

    ERIC Educational Resources Information Center

    Brody, Herb

    1985-01-01

    Although labor unions and inadequate technology play minor roles, the principal barrier to factory automation is "fear of change." Related problems include long-term benefits, nontechnical executives, and uncertainty of factory cost accounting. Industry support for university programs is helping to educate engineers to design, implement, and…

  20. Breaking Barriers: Overcoming Career Stereotyping in Early Childhood.

    ERIC Educational Resources Information Center

    Heathington, Betty S., Ed.

    The articles in this monograph are centered around a common concern: barriers created by career sex-stereotyping and the input of such stereotyping during the early years of a child's life. The first group of articles is composed of five discussion papers that provide insight into stereotyping existing in language, careers, toys, books, media, and…

  1. Teaching English Language Learners: Strategies for Overcoming Barriers

    ERIC Educational Resources Information Center

    Helfrich, Sara R.; Bosh, Amy J.

    2011-01-01

    The number of English language learners (ELLs) in today's classrooms is increasing. In this article, the authors identify four perceived barriers beginning and veteran teachers face in teaching literacy to ELLs: the lack of understanding of the role of literacy in other cultures, the teacher's inability to differentiate instruction to meet the…

  2. Teaching English Language Learners: Strategies for Overcoming Barriers

    ERIC Educational Resources Information Center

    Helfrich, Sara R.; Bosh, Amy J.

    2011-01-01

    The number of English language learners (ELLs) in today's classrooms is increasing. In this article, the authors identify four perceived barriers beginning and veteran teachers face in teaching literacy to ELLs: the lack of understanding of the role of literacy in other cultures, the teacher's inability to differentiate instruction to meet the…

  3. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    ERIC Educational Resources Information Center

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  4. Adolescents' Self-Efficacy to Overcome Barriers to Physical Activity Scale

    ERIC Educational Resources Information Center

    Dwyer, John J. M.; Chulak, Tala; Maitland, Scott; Allison, Kenneth R.; Lysy, Daria C.; Faulkner, Guy E. J.; Sheeshka, Judy

    2012-01-01

    This paper describes a revised measure of self-efficacy to overcome barriers to moderate and vigorous physical activity in a sample of 484 high school students in Toronto, Ontario. The students had a mean age of 15.3 years. Principal axis factoring with oblique rotation yielded five factors: self-efficacy to overcome internal, harassment, physical…

  5. Implementing District Energy Systems: Municipal Approaches To Overcoming Barriers

    NASA Astrophysics Data System (ADS)

    Simpson, Kevin George

    Climate change and energy security are issues facing municipalities throughout the world. Efficient, resilient, sustainable, community-based energy systems, such as district energy systems (DES), fuelled mostly by renewables, are an important tool for addressing both climate change and energy security at the municipal level. In spite of their benefits, DES are not widely adopted in Canada (CDEA, 2011). This is due to the complex nature of the barriers which project proponents face. This thesis examines the experience of the City of Prince George in adopting and implementing the Downtown DES. Using a case study methodology, data was collected through a review of relevant municipal documents and a series of semi-structured, open-ended interviews. A thematic analysis revealed unexpected barriers related to lack of adequate public consultation and negative perceptions regarding biomass as a fuel for the DES. These `lessons learned' were then developed into recommendations for other municipalities considering DES.

  6. Overcoming barriers in online workshop development: an ELITE experience.

    PubMed

    Talcott, Kimberly S; O'Donnell, John M; Burns, Helen K

    2013-06-01

    The Emerging Learning and Integrated Technologies Education (ELITE) Faculty Development Program created eight online workshops to assist nurse educators in using technology within their organization's nurse education program. Continuing education units were provided for completion of the individual online workshops. The ELITE program worked through several barriers to transform content that was previously presented during face-to-face workshops into standalone online offerings. Barriers and implementation strategies for the on-site to online transition included restructuring workshop objectives, keeping current with rapid technology changes, altering a course management system to meet the needs of the program and the learner, and crafting independent practice opportunities for the online learner. The online workshop development experience of the ELITE program may assist other continuing education and staff development professionals who are updating their program offerings or pursuing online education for the first time.

  7. No One Is Unemployable: Creative Solutions for Overcoming Barriers to Employment.

    ERIC Educational Resources Information Center

    Harney, Elisabeth E.

    The goal of the WorkNet Model Career Development & Job Placement for people with barriers is to help even the most challenged job seekers begin and advance in careers they enjoy. This paper presents one key component of the WorkNet Model, a practical process for creatively overcoming any barrier a candidate faces. The chapter includes: the…

  8. Overcoming barriers to public understanding of climate change

    NASA Astrophysics Data System (ADS)

    Hayhoe, K.

    2012-12-01

    Humans are interfering with global climate, increasing the risk of serious consequences for human society and the natural environment. As the scientific evidence builds, however, so does the public controversy surrounding this issue. Why is climate change so contentious? What makes it so hard to comprehend? I argue that there is no single reason for this, but rather a perfect storm of multiple confounding factors; scientific, historical, ideological, psychological and even physiological in nature. Education—of both the messengers and the audience—can play a critical role in surmounting many of the common barriers to understanding, accepting, and acting this important issue.

  9. Overcoming the barriers to using kangaroo care in neonatal settings.

    PubMed

    Penn, Sarah

    2015-06-01

    Skin-to-skin contact, or kangaroo care (KC), has benefits for babies and parents, improving clinical outcomes, temperature control, breastfeeding rates and child-parent bonding; it reduces morbidity and mortality. Barriers to KC for neonates may include a lack of training for nurses, lack of time, maternal or child physical or mental ill health, and inappropriate settings. With education and helpful management, neonatal nurses can advocate for KC for all babies. Parents may need information and encouragement to begin with. Therefore, nurses can improve the experiences of their patients and, in the long run, free time to perform clinical procedures.

  10. Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

    PubMed

    Rees, M A; Dunn, T B; Kuhr, C S; Marsh, C L; Rogers, J; Rees, S E; Cicero, A; Reece, L J; Roth, A E; Ekwenna, O; Fumo, D E; Krawiec, K D; Kopke, J E; Jain, S; Tan, M; Paloyo, S R

    2017-03-01

    Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

  11. The neuropathogenesis of feline immunodeficiency virus infection: Barriers to overcome

    PubMed Central

    Fletcher, Nicola F.; Meeker, Rick B.; Hudson, Lola C.; Callanan, John J.

    2010-01-01

    Feline immunodeficiency virus (FIV), like human immunodeficiency virus (HIV)-1, is a neurotropic lentivirus, and both natural and experimental infections are associated with neuropathology. FIV enters the brain early following experimental infection, most likely via the blood-brain and blood-cerebrospinal fluid barriers. The exact mechanism of entry, and the factors that influence this entry, are not fully understood. As FIV is a recognised model of HIV-1 infection, understanding such mechanisms is important, particularly as HIV enters the brain early in infection. Furthermore, the development of strategies to combat this central nervous system (CNS) infection requires an understanding of the interactions between the virus and the CNS. In this review the results of both in vitro and in vivo FIV studies are assessed in an attempt to elucidate the mechanisms of viral entry into the brain. PMID:20418131

  12. Staff resistance to restraint reduction: identifying & overcoming barriers.

    PubMed

    Curran, Staci Silver

    2007-05-01

    Professional organizations, regulating agencies, and hospital administrators have taken a strong stance on restraint reduction policies. When implementing a restraint reduction initiative, it is important to identify the barriers to restraint reduction, such as concern for personal safety, lack of knowledge about and practice using alternate de-escalation skills, and fear of disrupting the therapeutic milieu by using a variety of de-escalation methods. Education aimed to reduce the use of restraints needs to do more than simply provide information. It is important to acknowledge the emotional response of the nursing staff and the culture of the current practice. A variety of educational strategies, including role-playing, and case studies will help identify attitudes, beliefs, and behaviors that are congruent with reducing the use of restraints. If the ultimate goal of restraint reduction is philosophical change, it will eventually lead to a new culture of practice.

  13. Nanotechnologies: a strategy to overcome blood-brain barrier.

    PubMed

    De Rosa, Giuseppe; Salzano, Giuseppina; Caraglia, Michele; Abbruzzese, Alberto

    2012-01-01

    The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only selected molecules can passively diffuse to reach CNS. Drug pharmacokinetics and biodistribution can be changed by using nanotechnology, in order to improve drug accumulation into the action site and to limit the drug release in the healthy tissues. When the CNS diseases are characterised by BBB altered permeability, an enhanced drug delivery into the brain can be achieved by using nanocarriers. Moreover, modification of nanocarrier surface with specific endogenous or exogenous ligands can promote enhanced BBB crossing, also in case of unaltered endothelium. This review summarizes the most meaningful advances in the field of nanotechnology for brain delivery of therapeutics.

  14. Physical activity and exercise after stoma surgery: overcoming the barriers.

    PubMed

    Russell, Sarah

    2017-03-09

    This article presents the results from a large nationwide survey completed in 2016 that investigated the physical health and wellbeing of people living with stomas in the UK. In particular, the survey looked at physical activity and exercise, general attitudes and opinions about exercise, whether or not advice about physical activity had been received and other general questions about parastomal hernia and quality of life. There were 2631 respondents making it one of the largest known surveys to date. The findings were concerning yet unsurprising, highlighting a trend toward inactivity after stoma surgery and a fear of exercise in general. People also seem to have poor knowledge about appropriate activities, with many suggesting that the fear of developing a parastomal hernia is a major barrier to activity. Unsurprisingly, those who have a stoma owing to cancer seem to fare worse, reporting even lower levels of physical activity and worse quality of life compared to those with other conditions. This indicates that people who have a combination of a cancer diagnosis and also a stoma may need more specific or additional support in the longer term. The most concerning finding, however, was that the majority of patients could not recall being given any advice about exercise or physical activity by their nurse or surgeon. While this survey presents some initial findings, it raises questions for further research and work. It also highlights a significantly neglected area in both research and support for stoma patients and the health professionals caring for them.

  15. Overcoming nanoscale friction barriers in transition metal dichalcogenides

    NASA Astrophysics Data System (ADS)

    Cammarata, Antonio; Polcar, Tomas

    2017-08-01

    We study the atomic contributions to the nanoscale friction in layered M X2 (M =Mo , W; X =S , Se, Te) transition metal dichalcogenides by combining ab initio techniques with group-theoretical analysis. Starting from stable atomic configurations, we propose a computational method, named normal-modes transition approximation (NMTA), to individuate possible sliding paths from only the analysis of the phonon modes of the stable geometry. The method provides a way to decompose the atomic displacements realizing the layer sliding in terms of phonon modes of the stable structure, so as to guide the selection and tuning of specific atomic motions promoting M X2 sheets gliding, and to adjust the corresponding energy barrier. The present results show that main contributions to the nanoscale friction are due to few low frequency phonon modes, corresponding to rigid shifts of M X2 layers. We also provide further evidences that a previously reported Ti-doped MoS2 phase is a promising candidate as new material with enhanced tribologic properties. The NMTA approach can be exploited to tune the energetic and the structural features of specific phonon modes, and, thanks to its general formulation, can also be applied to any solid state system, irrespective of the chemical composition and structural topology.

  16. Mentoring women in academic surgery: overcoming institutional barriers to success.

    PubMed

    Hoover, Eddie L

    2006-09-01

    Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school are also women. This trend is likely to continue since women now earn 57% of all undergraduate degrees, and they earn more degrees in the health professions and biological sciences than men. Black and Hispanic women now earn 66% and 60% of bachelor's degrees in their respective ethnic groups. Overall, women are concentrated at the lowest faculty ranks at medical schools, with 70% holding the rank of instructor or assistant professor. Women continue to experience difficulty with recruitment, retention, promotion and pay issues compared to men. They also experience additional gender-specific issues, including primary responsibility for rearing families and quality-of-life issues in some specialties, including most of the surgical disciplines. Clearly, there is an evolving population shift at work here; the pool of candidates for medical school faculty positions is likely to be evenly split between men and women for Caucasians, Hispanics and Asians, while the African-American pool is likely heavily weighted in favor of the women. Women are beginning to garner more Latin honors recognition at graduation as well and the definition of the "best and the brightest" is being redefined. Therefore, institutions must continue to identify the barriers that deter women from entering surgery, to develop research tools to understand how to improve the process of developing leadership skills among women and to insure a "buy-in" of their male counterparts when components of the plan are being implemented.

  17. Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation.

    PubMed

    Tu, Haohua; Boppart, Stephen A

    2014-01-01

    Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring.

  18. Overcoming barriers to the employment and utilization of the nurse practitioner.

    PubMed

    Sullivan, J A; Dachelet, C Z; Sultz, H A; Henry, M; Carrol, H D

    1978-11-01

    A national longitudinal cohort study of nurse practitioners and their employers conducted during 1973--1976 provided data on barriers to the development of the nurse practitioner role in primary care. Nearly 90 per cent of the 500 primary care nurse practitioners responding and 75 per cent of the 407 employers responding reported encountering one or more barriers to the role development of the nurse practitioner in their practice setting. Nurse practitioners identified an average of 2.2 barriers and employers identified an average of 1.6 barriers each. Specific barriers identified by 20 per cent or more of the nurse practitioners and employers were legal restrictions, limitations of space and facilities, and resistance from other providers. The data and other evidence suggest that these barriers are not insurmountable and that progress is being made in overcoming these obstacles.

  19. Overcoming barriers to the employment and utilization of the nurse practitioner.

    PubMed Central

    Sullivan, J A; Dachelet, C Z; Sultz, H A; Henry, M; Carrol, H D

    1978-01-01

    A national longitudinal cohort study of nurse practitioners and their employers conducted during 1973--1976 provided data on barriers to the development of the nurse practitioner role in primary care. Nearly 90 per cent of the 500 primary care nurse practitioners responding and 75 per cent of the 407 employers responding reported encountering one or more barriers to the role development of the nurse practitioner in their practice setting. Nurse practitioners identified an average of 2.2 barriers and employers identified an average of 1.6 barriers each. Specific barriers identified by 20 per cent or more of the nurse practitioners and employers were legal restrictions, limitations of space and facilities, and resistance from other providers. The data and other evidence suggest that these barriers are not insurmountable and that progress is being made in overcoming these obstacles. PMID:717618

  20. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study.

    PubMed

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients' experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants' reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research.

  1. Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

    PubMed Central

    Barnicot, Kirsten; Couldrey, Laura; Sandhu, Sima; Priebe, Stefan

    2015-01-01

    Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research. PMID:26465757

  2. Measuring women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso

    PubMed Central

    2012-01-01

    Background In sub-Saharan Africa, women must overcome numerous barriers when they need modern healthcare. Respect of gender norms within the household and the community may still influence women's ability to obtain care. A lack of gender-sensitive instruments for measuring women's ability to overcome barriers compromises attempts to adequately quantify the burden and risk of exclusion they face when seeking modern healthcare. The aim of this study was to create and validate a synthetic measure of women's access to healthcare from a publicly available and possibly internationally comparable population-based survey. Method Seven questionnaire items from the Burkina Faso 2003 DHS were combined to create the index. Cronbach's alpha coefficient was used to test the reliability of the index. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were applied to evaluate the factorial structure and construct validity of the index while taking into account the hierarchical structure of the data. Results The index has a Cronbach's alpha of 0.75, suggesting adequate reliability. In EFA, three correlated factors fitted the data best. In CFA, the construct of perceived ability to overcome barriers to healthcare seeking emerged as a second-order latent variable with three domains: socioeconomic barriers, geographical barriers and psychosocial barriers. Model fit indices support the index's global validity for women of reproductive age in Burkina Faso. Evidence for construct validity comes from the finding that women's index scores increase with household living standard. Conclusion The DHS items can be combined into a reliable and valid, gender-sensitive index quantifying reproductive-age women's perceived ability to overcome barriers to healthcare seeking in Burkina Faso. The index complies conceptually with the sector-cross-cutting capability approach and enables measuring directly the perceived access to healthcare. Therefore it can help to improve the

  3. Strategies for Overcoming Key Barriers to Development of a National Security Workforce

    SciTech Connect

    2008-06-30

    This report documents the strategies for overcoming identified key barriers to development of an adequate national security workforce as part of the National Security Preparedness Project (NSPP) being performed under a Department of Energy (DOE) National Nuclear Security Administration (NNSA) grant. Many barriers currently exist that prevent the development of an adequate number of properly trained national security personnel. The identified strategies to address the barriers will focus on both short-term and long-term efforts, as well as strategies to capture legacy knowledge of retiring national security workforce personnel.

  4. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, P. C.; Halverson, M. A.

    2013-09-01

    This guidance document was prepared using the input from the meeting summarized in the draft CSI Roadmap to provide Building America research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America innovations arising in and/or stemming from codes, standards, and rating methods.

  5. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    ERIC Educational Resources Information Center

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  6. Powering Your Community With Solar: Overcoming Market and Implementation Barriers (Fact Sheet)

    SciTech Connect

    Not Available

    2012-06-01

    This document introduces the Energy Department's new Solarize Guidebook: A Community Guide to Collective Purchasing of Residential PV Systems. The guide is designed for 'green' consumers, utilities, local governments, and community groups who want to replicate the success of the Solarize Portland model, overcome barriers to implementation, and permanently transform the market for solar energy in their communities.

  7. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2013-10-01

    Spinal Cord Cell Transplantation for ALS PRINCIPAL INVESTIGATOR: Nicholas Boulis CONTRACTING ORGANIZATION: Emory University...COVERED 30September2012–29September2013 4. TITLE AND SUBTITLE Overcoming the Practical Barriers to Spinal Cord Cell Transplantation 5a. CONTRACT...injections. At the same time, little is understood about the appropriate immunosuppressive therapy for spinal cord stem cell transplant recipients. In our

  8. Using Appropriate Digital Tools to Overcome Barriers to Collaborative Learning in Classrooms

    ERIC Educational Resources Information Center

    Wardlow, Liane; Harm, Eian

    2015-01-01

    Collaborative learning provides students with vital opportunities to create and build knowledge. Existing technologies can facilitate collaborative learning. However, barriers exist to enacting collaborative practices related to the coverage of material for assessments and classroom management concerns, among others. Teachers can overcome these…

  9. Critical elements for eco-retrofitting a conventional industrial park: Social barriers to be overcome.

    PubMed

    Ceglia, Domenico; Abreu, Mônica Cavalcanti Sá de; Da Silva Filho, José Carlos Lázaro

    2017-02-01

    This paper aims to explore critical elements for eco-retrofitting a conventional industrial park, based on a survey of companies and institutions located in Brazil. The study investigates social barriers to be overcome in promotion of opportunities for waste exchange. Our results indicate that values, trust behaviour, waste cognitive domain and environment engagement are necessary for the creation of an eco-industrial park. Similar values of benevolence and universalism are essential for company engagement to eco-retrofit. Low levels of trust behaviour combining with limited waste cognitive domain prevent firms from establishing agreement on waste exchange initiatives. The findings lend support to the view that social barriers are pre-requisites to engagement among firms in establishing technological and logistical solutions. Serious attention needs to be given to these social barriers because they are not easily overcome in the social and economic context of developing countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Identifying and overcoming the barriers to bedside rounds: a multicenter qualitative study.

    PubMed

    Gonzalo, Jed D; Heist, Brian S; Duffy, Briar L; Dyrbye, Liselotte; Fagan, Mark J; Ferenchick, Gary; Harrell, Heather; Hemmer, Paul A; Kernan, Walter N; Kogan, Jennifer R; Rafferty, Colleen; Wong, Raymond; Elnicki, D Michael

    2014-02-01

    The use of bedside rounds in teaching hospitals has declined, despite recommendations from educational leaders to promote this effective teaching strategy. The authors sought to identify reasons for the decrease in bedside rounds, actual barriers to bedside rounds, methods to overcome trainee apprehensions, and proposed strategies to educate faculty. A qualitative inductive thematic analysis using transcripts from audio-recorded, semistructured telephone interviews with a purposive sampling of 34 inpatient attending physicians from 10 academic U.S. institutions who met specific inclusion criteria for "bedside rounds" was performed in 2010. Main outcomes were themes pertaining to barriers, methods to overcome trainee apprehensions, and strategies to educate faculty. Quotations highlighting themes are reported. Half of respondents (50%) were associate or full professors, averaging 14 years in academic medicine. Primary reasons for the perceived decline in bedside rounds were physician- and systems related, although actual barriers encountered related to systems, time, and physician-specific issues. To address resident apprehensions, six themes were identified: build partnerships, create safe learning environments, overcome with experience, make bedside rounds educationally worthwhile, respect trainee time, and highlight positive impact on patient care. Potential strategies for educating faculty were identified, most commonly faculty development initiatives, divisional/departmental culture change, and one-on-one shadowing opportunities. Bedside teachers encountered primarily systems- and time-related barriers and overcame resident apprehensions by creating a learner-oriented environment. Strategies used by experienced bedside teachers can be used for faculty development aimed at promoting bedside rounds.

  11. Overcoming barriers to exercise among parents: a social cognitive theory perspective.

    PubMed

    Mailey, Emily L; Phillips, Siobhan M; Dlugonski, Deirdre; Conroy, David E

    2016-08-01

    Parents face numerous barriers to exercise and exhibit high levels of inactivity. Examining theory-based determinants of exercise among parents may inform interventions for this population. The purpose of this study was to test a social-cognitive model of parental exercise participation over a 12-month period. Mothers (n = 226) and fathers (n = 70) of children <16 completed measures of exercise, barriers self-efficacy, perceived barriers, and exercise planning at baseline and 1 year later. Panel analyses were used to test the hypothesized relationships. Barriers self-efficacy was related to exercise directly and indirectly through perceived barriers and prioritization/planning. Prioritization and planning also mediated the relationship between perceived barriers and exercise. These paths remained significant at 12 months. These results suggest efforts to increase exercise in parents should focus on improving confidence to overcome exercise barriers, reducing perceptions of barriers, and helping parents make specific plans for prioritizing and engaging in exercise.

  12. Overcoming cultural barriers to diabetes control: a qualitative study of southwestern New Mexico Hispanics.

    PubMed

    McCloskey, Joanne; Flenniken, Donna

    2010-01-01

    This qualitative study examined the impact of cultural barriers on self-management of diabetes among Hispanic participants in LA VIDA (Lifestyle and Values Impact Diabetes Awareness), a diabetes intervention program in southwestern New Mexico. As part of the LA VIDA program evaluation, in depth interviews were conducted with 50 Hispanics who had participated in one or more activities, including diabetes education classes, grocery store tours, and support groups, and who had interacted with promotores (community health workers). LA VIDA participants reported that a sense of empowerment and increased self-efficacy enabled them to overcome cultural barriers related to the traditional Hispanic diet, lack of social support, and denial about having diabetes.

  13. Overcoming or circumventing the stratum corneum barrier for efficient transcutaneous immunization.

    PubMed

    Chen, Zhongjian; Lu, Yongjiu; Qi, Jianping; Zhu, Quangang; Lu, Yi; Wu, Wei

    2017-10-05

    Transcutaneous immunization (TCI) is a promising alternative to vaccine delivery via the subcutaneous and intramuscular routes because of the unique immunological characteristics of the skin. However, the stratum corneum (SC) prevents entry of most therapeutic compounds into the body. Several physical devices have been developed to overcome the SC barrier, but still damage the skin. However, by targeting antigens to the abundant perifollicular antigen-presenting cells (APCs), the transfollicular route might be a promising approach for TCI without compromising the skin barrier. Copyright © 2017. Published by Elsevier Ltd.

  14. Overcoming barriers to recruiting ethnic minorities to mental health research: a typology of recruitment strategies.

    PubMed

    Waheed, Waquas; Hughes-Morley, Adwoa; Woodham, Adrine; Allen, Gill; Bower, Peter

    2015-05-02

    The ethnic minority population in developed countries is increasing over time. These groups are at higher risk of mental illness and demonstrate lower participation in research. Published evidence suggests that multiple factors like stigma, lack of trust, differences in explanatory models, logistical issues and lack of culturally aware researchers act as barriers to ethnic minority recruitment into mental health research. To reduce inequalities in participation, there is a need to devise innovative and culturally sensitive recruitment strategies. It is important that researchers share their experience of employing these strategies so that ethnic minority participation can be facilitated. We previously published a systematic review of barriers to recruiting ethnic minority participants into mental health research. The nine papers included in our prior review formed the basis for developing a typology of barriers to recruiting ethnic minorities into mental health research. This typology identified 33 barriers, described under five themes. We further extracted data on the strategies used to overcome these recruitment barriers, as described in the included studies. The strategies employed by the authors could be matched to all but two barriers (psychopathology/substance misuse and limited resource availability). There was evidence that multiple strategies were employed, and that these depended upon the population, clinical set-up and resources available. This typology of strategies to overcome barriers to recruiting ethnic minorities provides guidance on achieving higher rates of recruitment. It is important that researchers plan to deploy these strategies well in advance of initiating recruitment. Whilst adopting these strategies, the authors have not been able to quantify the positive impact of these strategies on recruitment. The typology should encourage researchers to employ these strategies in future research, refine them further and quantitatively evaluate their

  15. Coherent anti-Stokes Raman scattering microscopy: overcoming technical barriers for clinical translation

    PubMed Central

    Tu, Haohua; Boppart, Stephen A.

    2015-01-01

    Clinical translation of coherent anti-Stokes Raman scattering microscopy is of great interest because of the advantages of noninvasive label-free imaging, high sensitivity, and chemical specificity. For this to happen, we have identified and review the technical barriers that must be overcome. Prior investigations have developed advanced techniques (features), each of which can be used to effectively overcome one particular technical barrier. However, the implementation of one or a small number of these advanced features in previous attempts for clinical translation has often introduced more tradeoffs than benefits. In this review, we outline a strategy that would integrate multiple advanced features to overcome all the technical barriers simultaneously, effectively reduce tradeoffs, and synergistically optimize CARS microscopy for clinical translation. The operation of the envisioned system incorporates coherent Raman micro-spectroscopy for identifying vibrational biomolecular markers of disease and single-frequency (or hyperspectral) Raman imaging of these specific biomarkers for real-time in vivo diagnostics and monitoring. An optimal scheme of clinical CARS micro-spectroscopy for thin ex vivo tissues. PMID:23674234

  16. Public Health in the Emergency Department: Overcoming Barriers to Implementation and Dissemination

    PubMed Central

    McKay, Mary Pat; Vaca, Federico E.; Field, Craig; Rhodes, Karin

    2011-01-01

    This article is the outcome of a consensus building workshop entitled, “Overcoming Barriers to Implementation and Dissemination” convened at the 2009 Academic Emergency Medicine Consensus Conference, “Public Health in the ED: Surveillance, Screening, and Intervention.” The participants were asked to address potential methods for overcoming barriers to the dissemination and implementation in the emergency department (ED) of evidenced-based practices to improve public health. The panel discussed three broad areas of interest including methods for disseminating evidence-based practices, barriers encountered during the process of implementation, and the importance of involvement in activities outside the ED including engagement in policy development and improvement. Four recommendations were discussed in detail and consensus was reached. The recommendations included 1) researchers and advocates should disseminate findings through multiple forums beyond peer-reviewed publications when an ED-based public health intervention has enough evidence to support integration into the routine practice of emergency care; 2) local barriers to implementation of public health interventions should be recognized and well understood from multiple perspectives prior to implementation; 3) innovation must be put into place and adapted based on local institutional context and culture as barriers and the best methods for overcoming them will vary across institutions; and 4) use of legislation, regulation, and incentives outside of the ED should support and strengthen ED-based interventions. For each area of interest, research dimensions to extend the current understanding of methods for effectively and efficiently implementing evidence-based public health interventions in the ED were discussed and consensus was achieved. PMID:20053233

  17. Overcoming the Cystic Fibrosis Sputum Barrier to Leading Adeno-associated Virus Gene Therapy Vectors

    PubMed Central

    Schuster, Benjamin S; Kim, Anthony J; Kays, Joshua C; Kanzawa, Mia M; Guggino, William B; Boyle, Michael P; Rowe, Steven M; Muzyczka, Nicholas; Suk, Jung Soo; Hanes, Justin

    2014-01-01

    Gene therapy has not yet improved cystic fibrosis (CF) patient lung function in human trials, despite promising preclinical studies. In the human CF lung, inhaled gene vectors must penetrate the viscoelastic secretions coating the airways to reach target cells in the underlying epithelium. We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials. Using multiple particle tracking, we found that sputum strongly impeded diffusion of AAV, regardless of serotype, by adhesive interactions and steric obstruction. Approximately 50% of AAV vectors diffused >1,000-fold more slowly in sputum than in water, with large patient-to-patient variation. We thus tested two strategies to improve AAV diffusion in sputum. We showed that an AAV2 mutant engineered to have reduced heparin binding diffused twice as fast as AAV2 on average, presumably because of reduced adhesion to sputum. We also discovered that the mucolytic N-acetylcysteine could markedly enhance AAV diffusion by altering the sputum microstructure. These studies underscore that sputum is a major barrier to CF gene delivery, and offer strategies for increasing AAV penetration through sputum to improve clinical outcomes. PMID:24869933

  18. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers.

  19. How to Overcome Barriers and Establish a Successful Home HD Program

    PubMed Central

    Chan, Christopher; Blagg, Christopher; Lockridge, Robert; Golper, Thomas; Finkelstein, Fred; Shaffer, Rachel; Mehrotra, Rajnish

    2012-01-01

    Summary Home hemodialysis (HD) is an underused dialysis modality in the United States, even though it provides an efficient and probably cost-effective way to provide more frequent or longer dialysis. With the advent of newer home HD systems that are easier for patients to learn, use, and maintain, patient and provider interest in home HD is increasing. Although barriers for providers are similar to those for peritoneal dialysis, home HD requires more extensive patient training, nursing education, and infrastructure support in order to maintain a successful program. In addition, because many physicians and patients do not have experience with home HD, reluctance to start home HD programs is widespread. This in-depth review describes barriers to home HD, focusing on patients, individual physicians and practices, and dialysis facilities, and offers suggestions for how to overcome these barriers and establish a successful home HD program. PMID:23037981

  20. "Closing the Loop": Overcoming barriers to locally sourcing food in Fort Collins, Colorado

    NASA Astrophysics Data System (ADS)

    DeMets, C. M.

    2012-12-01

    Environmental sustainability has become a focal point for many communities in recent years, and restaurants are seeking creative ways to become more sustainable. As many chefs realize, sourcing food locally is an important step towards sustainability and towards building a healthy, resilient community. Review of literature on sustainability in restaurants and the local food movement revealed that chefs face many barriers to sourcing their food locally, but that there are also many solutions for overcoming these barriers that chefs are in the early stages of exploring. Therefore, the purpose of this research is to identify barriers to local sourcing and investigate how some restaurants are working to overcome those barriers in the city of Fort Collins, Colorado. To do this, interviews were conducted with four subjects who guide purchasing decisions for restaurants in Fort Collins. Two of these restaurants have created successful solutions and are able to source most of their food locally. The other two are interested in and working towards sourcing locally but have not yet been able to overcome barriers, and therefore only source a few local items. Findings show that there are four barriers and nine solutions commonly identified by each of the subjects. The research found differences between those who source most of their food locally and those who have not made as much progress in local sourcing. Based on these results, two solution flowcharts were created, one for primary barriers and one for secondary barriers, for restaurants to assess where they are in the local food chain and how they can more successfully source food locally. As there are few explicit connections between this research question and climate change, it is important to consider the implicit connections that motivate and justify this research. The question of whether or not greenhouse gas emissions are lower for locally sourced food is a topic of much debate, and while there are major developments

  1. Overcoming early barriers to PCMH practice improvement in family medicine residencies.

    PubMed

    Fernald, Douglas H; Deaner, Nicole; O'Neill, Caitlin; Jortberg, Bonnie T; degruy, Frank Verloin; Dickinson, W Perry

    2011-01-01

    Residency programs face inevitable challenges as they redesign their practices for higher quality care and resident training. Identifying and addressing early barriers can help align priorities and thereby augment the capacity to change. Evaluation of the Colorado Family Medicine Residency PCMH Project included iterative qualitative analysis of field notes, interviews, and documents to identify early barriers to change and strategies to overcome them. Nine common but not universal barriers were identified: (1) a practice's history reflected some negative past experiences with quality improvement or routines incompatible with transformative change, (2) leadership gaps were evident in unprepared practice leaders or hierarchical leadership, (3) resistance and skepticism about change were expressed through cynicism aimed at change or ability to change, (4) unproductive team processes were reflected in patterns of canceled meetings, absentee leaders, or lack of accountability, (5) knowledge gaps about the Patient-centered Medical Home (PCMH) were apparent from incomplete dissemination about the project or planned changes, (6) EHR implementation distracted focus or stalled improvement activity, (7) sponsoring organizations' constraints emerged from staffing rules and differing priorities, (8) insufficient staff participation resulted from traditional role expectations and structures, and (9) communication was hampered by ineffective methods and part-time faculty and residents. Early barriers responded to varying degrees to specific interventions by practice coaches. Some barriers that interfere with practices getting started with cultural and structural transformation can be addressed with persistent attention and reflection from on-site coaches and by realigning the talents, leaders, and priorities already in these residency programs.

  2. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    PubMed Central

    Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. Results Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. Conclusions A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders. PMID:26262941

  3. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers.

    PubMed

    Justice, Laura M; Logan, Jessica R; Damschroder, Laura

    2015-12-01

    This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their children with language impairment (LI). The authors examined caregiver-level data corresponding to implementation issues from two randomized controlled trials and mapped these to domains in the TDF as well as empirically validated behavior-change techniques. Four barriers to implementation were identified as potentially affecting caregivers' implementation: time pressures, reading difficulties, discomfort with reading, and lack of awareness of benefits. These were mapped to 3 TDF domains: intentions, beliefs about capabilities, and skills. In turn, 4 behavior-change techniques were identified as potential vehicles for affecting these domains: reward, feedback, model, and encourage. An ongoing study is described that is determining the effects of these techniques for improving caregivers' implementation of a shared-reading intervention. A description of the steps to identifying barriers to implementation, in conjunction with an ongoing experiment that will explicitly determine whether behavior-change techniques affect these barriers, provides a model for how implementation science can be used to identify and overcome implementation barriers in the treatment of communication disorders.

  4. Implementing a resident research program to overcome barriers to resident research.

    PubMed

    Rothberg, Michael B; Kleppel, Reva; Friderici, Jennifer L; Hinchey, Kevin

    2014-08-01

    Internal medicine residents are required to participate in scholarly activity, but conducting original research during residency is challenging. Following a poor Match at Baystate Medical Center, the authors implemented a resident research program to overcome known barriers to resident research. The multifaceted program addressed the following barriers: lack of interest, lack of time, insufficient technical support, and paucity of mentors. The program consisted of evidence-based medicine training to stimulate residents' interest in research and structural changes to support their conduct of research, including protected time for research during ambulatory blocks, a research assistant to help with tasks such as institutional review board applications and data entry, a research nurse to help with data collection, easily accessible biostatistical support, and a resident research director to provide mentorship. Following implementation in the fall of 2005, there was a steady rise in the number of resident presentations at national meetings, then in the number of resident publications. From 2001 to 2006, the department saw 3 resident publications. From 2006 to 2012, that number increased to 39 (P< .001). The department also saw more original research (29 publications) and resident first authors (12 publications) after program implementation. The percentage of residents accepted into fellowships rose from 33% before program implementation to 49% after (P = .04). This comprehensive resident research program, which focused on evidence-based medicine and was tailored to overcome specific barriers, led to a significant increase in the number of resident Medline publications and improved the reputation of the residency program.

  5. Geothermal(Ground-Source)Heat Pumps: Market Status, Barriers to Adoption, and Actions to Overcome Barriers

    SciTech Connect

    Hughes, Patrick

    2008-12-01

    More effective stewardship of our resources contributes to the security, environmental sustainability, and economic well-being of the nation. Buildings present one of the best opportunities to economically reduce energy consumption and limit greenhouse gas emissions. Geothermal heat pumps (GHPs), sometimes called ground-source heat pumps, have been proven capable of producing large reductions in energy use and peak demand in buildings. However, GHPs have received little attention at the policy level as an important component of a national strategy. Have policymakers mistakenly overlooked GHPs, or are GHPs simply unable to make a major contribution to the national goals for various reasons? This brief study was undertaken at DOE's request to address this conundrum. The scope of the study includes determining the status of global GHP markets and the status of the GHP industry and technology in the United States, assembling previous estimates of GHP energy savings potential, identifying key barriers to application of GHPs, and identifying actions that could accelerate market adoption of GHPs. The findings are documented in this report along with conclusions and recommendations.

  6. Hedgehog Signaling Overcomes an EZH2-Dependent Epigenetic Barrier to Promote Cholangiocyte Expansion

    PubMed Central

    Lu, Jie; Almada, Luciana L.; Lomberk, Gwen; Fernandez-Zapico, Martin E.; Urrutia, Raul; Huebert, Robert C.

    2016-01-01

    Background & Aims Developmental morphogens play an important role in coordinating the ductular reaction and portal fibrosis occurring in the setting of cholangiopathies. However, little is known about how membrane signaling events in ductular reactive cells (DRCs) are transduced into nuclear transcriptional changes to drive cholangiocyte maturation and matrix deposition. Therefore, the aim of this study was to investigate potential mechanistic links between cell signaling events and epigenetic regulators in DRCs. Methods Using directed differentiation of induced pluripotent stem cells (iPSC), isolated DRCs, and in vivo models, we examine the mechanisms whereby sonic hedgehog (Shh) overcomes an epigenetic barrier in biliary precursors and promotes both cholangiocyte maturation and deposition of fibronectin (FN). Results We demonstrate, for the first time, that Gli1 influences the differentiation state and fibrogenic capacity of iPSC-derived hepatic progenitors and isolated DRCs. We outline a novel pathway wherein Shh-mediated Gli1 binding in key cholangiocyte gene promoters overcomes an epigenetic barrier conferred by the polycomb protein, enhancer of zeste homolog 2 (EZH2) and initiates the transcriptional program of cholangiocyte maturation. We also define previously unknown functional Gli1 binding sites in the promoters of cytokeratin (CK)7, CK19, and FN. Our in vivo results show that EZH2 KO mice fed the choline-deficient, ethanolamine supplemented (CDE) diet have an exaggerated cholangiocyte expansion associated with more robust ductular reaction and increased peri-portal fibrosis. Conclusion We conclude that Shh/Gli1 signaling plays an integral role in cholangiocyte maturation in vitro by overcoming an EZH2-dependent epigenetic barrier and this mechanism also promotes biliary expansion in vivo. PMID:27936185

  7. Exploring How Lay Rescuers Overcome Barriers to Provide Cardiopulmonary Resuscitation: A Qualitative Study.

    PubMed

    Mathiesen, Wenche Torunn; Bjørshol, Conrad Arnfinn; Høyland, Sindre; Braut, Geir Sverre; Søreide, Eldar

    2017-02-01

    Survival rates after out-of-hospital cardiac arrest (OHCA) vary considerably among regions. The chance of survival is increased significantly by lay rescuer cardiopulmonary resuscitation (CPR) before Emergency Medical Services (EMS) arrival. It is well known that for bystanders, reasons for not providing CPR when witnessing an OHCA incident may be fear and the feeling of being exposed to risk. The aim of this study was to gain a better understanding of why barriers to providing CPR are overcome. Using a semi-structured interview guide, 10 lay rescuers were interviewed after participating in eight OHCA incidents. Qualitative content analysis was used. The lay rescuers were questioned about their CPR-knowledge, expectations, and reactions to the EMS and from others involved in the OHCA incident. They also were questioned about attitudes towards providing CPR in an OHCA incident in different contexts. The lay rescuers reported that they were prepared to provide CPR to anybody, anywhere. Comprehending the severity in the OHCA incident, both trained and untrained lay rescuers provided CPR. They considered CPR provision to be the expected behavior of any community citizen and the EMS to act professionally and urgently. However, when asked to imagine an OHCA in an unclear setting, they revealed hesitation about providing CPR because of risk to their own safety. Mutual trust between community citizens and towards social institutions may be reasons for overcoming barriers in providing CPR by lay rescuers. A normative obligation to act, regardless of CPR training and, importantly, without facing any adverse legal reactions, also seems to be an important factor behind CPR provision. Mathiesen WT , Bjørshol CA , Høyland S , Braut GS , Søreide E . Exploring how lay rescuers overcome barriers to provide cardiopulmonary resuscitation: a qualitative study. Prehosp Disaster Med. 2017;32(1):27-32.

  8. Overcoming barriers in topical administration of gold nanoparticles for optical coherence tomography using multimodal delivery

    NASA Astrophysics Data System (ADS)

    Kim, Chang Soo; Wilder-Smith, Petra; Ahn, Yeh-Chan; Liaw, Lih-Huei L.; Chen, Zhongping; Kwon, Young Jik

    2010-02-01

    Optical coherence tomography (OCT) is a non-invasive and promising imaging modality with high resolution that is an order of magnitude higher than current diagnostic techniques. However, its use in detecting early-stage cancer is limited due to insufficient contrast level in biological tissue, which can be enhanced by harnessing contrast agents [e.g., gold nanoparticles (Au NPs)]. Enhanced penetration by creating micropassages and distribution by ultrasonic force (multimodal topical delivery) was proven to overcome two major barriers (stratum corneum and epithelial barriers) in topically administering Au NPs using an in vivo oral dysplasia hamster model (overall 150% enhanced OCT contrast). Expanded progress on a highly efficient and versatile Au NP-releasing polymer microneedle platform showed a promising next generation multi-modal delivery of Au NPs.

  9. Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers

    PubMed Central

    Liu, Jian-ping; Wang, Ting-ting; Wang, Dang-ge; Dong, An-jie; Li, Ya-ping; Yu, Hai-jun

    2017-01-01

    The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment. PMID:27569390

  10. Overcoming barriers to high performance seismic design using lessons learned from the green building industry

    NASA Astrophysics Data System (ADS)

    Glezil, Dorothy

    NEHRP's Provisions today currently governing conventional seismic resistant design. These provisions, though they ensure the life-safety of building occupants, extensive damage and economic losses may still occur in the structures. This minimum performance can be enhanced using the Performance-Based Earthquake Engineering methodology and passive control systems like base isolation and energy dissipation systems. Even though these technologies and the PBEE methodology are effective reducing economic losses and fatalities during earthquakes, getting them implemented into seismic resistant design has been challenging. One of the many barriers to their implementation has been their upfront costs. The green building community has faced some of the same challenges that the high performance seismic design community currently faces. The goal of this thesis is to draw on the success of the green building industry to provide recommendations that may be used overcome the barriers that high performance seismic design (HPSD) is currently facing.

  11. Identifying, understanding and overcoming barriers to medication error reporting in hospitals: a focus group study.

    PubMed

    Hartnell, Nicole; MacKinnon, Neil; Sketris, Ingrid; Fleming, Mark

    2012-05-01

    The under-reporting of medication errors can compromise patient safety. A qualitative study was conducted to enhance the understanding of barriers to medication error reporting in healthcare organisations. Focus groups (with physicians, pharmacists and nurses) and in-depth interviews (with risk managers) were used to identify medication error reporting beliefs and practices at four community hospitals in Nova Scotia, Canada. Audio tapes were transcribed verbatim and analysed for thematic content using the template style of analysis. The development and analysis of this study were guided by Safety Culture Theory. Incentives for medication error reporting were thematised into three categories: patient protection, provider protection and professional compliance. Barriers to medication error reporting were thematised into five categories: reporter burden, professional identity, information gap, organisational factors and fear. Facilitators to encourage medication error reporting were classified into three categories: reducing reporter burden, closing the communication gap and educating for success. Participants indicated they would report medication errors more frequently if reporting were made easier, if they were adequately educated about reporting, and if they received timely feedback. Study results may lead to a better understanding of the barriers to medication error reporting, why these barriers exist and what can be done to successfully overcome them. These results could be used by hospitals to encourage reporting of medication errors and ultimately make organisational changes leading to a reduction in the incidence of medication errors and an improvement in patient safety.

  12. Overcoming Codes and Standards Barriers to Innovations in Building Energy Efficiency

    SciTech Connect

    Cole, Pamala C.; Gilbride, Theresa L.

    2015-02-15

    In this journal article, the authors discuss approaches to overcoming building code barriers to energy-efficiency innovations in home construction. Building codes have been a highly motivational force for increasing the energy efficiency of new homes in the United States in recent years. But as quickly as the codes seem to be changing, new products are coming to the market at an even more rapid pace, sometimes offering approaches and construction techniques unthought of when the current code was first proposed, which might have been several years before its adoption by various jurisdictions. Due to this delay, the codes themselves can become barriers to innovations that might otherwise be helping to further increase the efficiency, comfort, health or durability of new homes. . The U.S. Department of Energy’s Building America, a program dedicated to improving the energy efficiency of America’s housing stock through research and education, is working with the U.S. housing industry through its research teams to help builders identify and remove code barriers to innovation in the home construction industry. The article addresses several approaches that builders use to achieve approval for innovative building techniques when code barriers appear to exist.

  13. Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier.

    PubMed

    Mänz, Benjamin; Schwemmle, Martin; Brunotte, Linda

    2013-07-01

    Avian influenza A viruses, such as the highly pathogenic avian H5N1 viruses, sporadically enter the human population but often do not transmit between individuals. In rare cases, however, they establish a new lineage in humans. In addition to well-characterized barriers to cell entry, one major hurdle which avian viruses must overcome is their poor polymerase activity in human cells. There is compelling evidence that these viruses overcome this obstacle by acquiring adaptive mutations in the polymerase subunits PB1, PB2, and PA and the nucleoprotein (NP) as well as in the novel polymerase cofactor nuclear export protein (NEP). Recent findings suggest that synthesis of the viral genome may represent the major defect of avian polymerases in human cells. While the precise mechanisms remain to be unveiled, it appears that a broad spectrum of polymerase adaptive mutations can act collectively to overcome this defect. Thus, identification and monitoring of emerging adaptive mutations that further increase polymerase activity in human cells are critical to estimate the pandemic potential of avian viruses.

  14. Overcoming the Barriers to Pharmacist Intervention in Problems Associated with the Use of Drugs--Institutional Pharmacy.

    ERIC Educational Resources Information Center

    Baumgartner, R. Paul, Jr.

    1979-01-01

    Barriers to role expansion for pharmacists working in institutional settings are discussed, such as competency, interdisciplinary responsibilities, and financial reimbursement. Underlying principles that may be applied to overcome the traditional barriers to pharmacist intervention in drug use problems are examined. (SF)

  15. Overcoming barriers to diabetes care: Perceived communication issues of healthcare professionals attending a pilot Diabetes UK training programme.

    PubMed

    Mosely, Kylie; Aslam, Aysha; Speight, Jane

    2010-02-01

    As part of our evaluation of the Diabetes UK Careline workshop "Overcoming barriers to diabetes care", we received feedback from 18 healthcare professionals. Generally, they felt competent in identifying patients' psychosocial issues but less knowledgeable/skilled in handling them. Lack of time, privacy and support were barriers to addressing patients' psychosocial concerns. 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Overcoming Barriers: Adolescents’ Experiences Using a Mobile Phone Dietary Assessment App

    PubMed Central

    Svensson, Åsa; Magnusson, Maria

    2016-01-01

    Background The use of new technology has the potential to increase participation rates in dietary studies and improve the validity of collected dietary data. However, to evaluate the usability of developed dietary methods, qualitative studies of participants’ experiences and perceptions are needed. Objective To explore adolescents’ experiences using a newly developed mobile phone dietary assessment app, with a focus on factors that could affect their recording of dietary intake. Methods Focus group interviews were conducted with 75 participants who had used a newly developed mobile phone dietary assessment app in a quantitative evaluation study. The interviews were analyzed using qualitative content analysis and the theoretical framework of Self Determination Theory was applied. Results The adolescents’ use of the mobile phone dietary assessment app was characterized by their struggle to overcome several perceived barriers. Facilitators that helped adolescents complete the method were also identified. Motivation was found to be an important facilitator, and intrinsically motivated participants completed the method because they found it fun to use. The autonomous extrinsically motivated participants completed the method for the greater good, in order to contribute to the study. The controlled extrinsically motivated participants completed the method to get a reward or avoid punishment. Amotivated participants did not complete the method. More motivated participants were assumed to be more able to overcome barriers and needed less facilitators. Conclusions Future studies that examine the recording of food intake should include systematic efforts that aim to minimize identified barriers and promote identified facilitators. Further research should specifically aim at studying methods for (and effects of) increasing intrinsic motivation by supporting autonomy, competence, and relatedness among adolescents asked to participate in dietary studies. PMID:27473462

  17. Overcoming Barriers: Adolescents' Experiences Using a Mobile Phone Dietary Assessment App.

    PubMed

    Svensson, Åsa; Magnusson, Maria; Larsson, Christel

    2016-07-29

    The use of new technology has the potential to increase participation rates in dietary studies and improve the validity of collected dietary data. However, to evaluate the usability of developed dietary methods, qualitative studies of participants' experiences and perceptions are needed. To explore adolescents' experiences using a newly developed mobile phone dietary assessment app, with a focus on factors that could affect their recording of dietary intake. Focus group interviews were conducted with 75 participants who had used a newly developed mobile phone dietary assessment app in a quantitative evaluation study. The interviews were analyzed using qualitative content analysis and the theoretical framework of Self Determination Theory was applied. The adolescents' use of the mobile phone dietary assessment app was characterized by their struggle to overcome several perceived barriers. Facilitators that helped adolescents complete the method were also identified. Motivation was found to be an important facilitator, and intrinsically motivated participants completed the method because they found it fun to use. The autonomous extrinsically motivated participants completed the method for the greater good, in order to contribute to the study. The controlled extrinsically motivated participants completed the method to get a reward or avoid punishment. Amotivated participants did not complete the method. More motivated participants were assumed to be more able to overcome barriers and needed less facilitators. Future studies that examine the recording of food intake should include systematic efforts that aim to minimize identified barriers and promote identified facilitators. Further research should specifically aim at studying methods for (and effects of) increasing intrinsic motivation by supporting autonomy, competence, and relatedness among adolescents asked to participate in dietary studies.

  18. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier.

    PubMed

    Di Gioia, Sante; Trapani, Adriana; Castellani, Stefano; Carbone, Annalucia; Belgiovine, Giuliana; Craparo, Emanuela Fabiola; Puglisi, Giovanni; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2015-10-01

    Gene therapy, i.e. the delivery and expression of therapeutic genes, holds great promise for congenital and acquired respiratory diseases. Non-viral vectors are less toxic and immunogenic than viral vectors, although they are characterized by lower efficiency. However, they have to overcome many barriers, including inflammatory and immune mediators and cells. The respiratory and airway epithelial cells, the main target of these vectors, are coated with a layer of mucus, which hampers the effective reaching of gene therapy vectors carrying either plasmid DNA or small interfering RNA. This barrier is thicker in many lung diseases, such as cystic fibrosis. This review summarizes the most important advancements in the field of non-viral vectors that have been achieved with the use of nanoparticulate (NP) systems, composed either of polymers or lipids, in the lung gene delivery. In particular, different strategies of targeting of respiratory and airway lung cells will be described. Then, we will focus on the two approaches that attempt to overcome the mucus barrier: coating of the nanoparticulate system with poly(ethylene glycol) and treatment with mucolytics. Our conclusions are: 1) Ligand and physical targeting can direct therapeutic gene expression in specific cell types in the respiratory tract; 2) Mucopenetrating NPs are endowed with promising features to be useful in treating respiratory diseases and should be now advanced in pre-clinical trials. Finally, we discuss the development of such polymer- and lipid-based NPs in the context of in vitro and in vivo disease models, such as lung cancer, as well as in clinical trials.

  19. Teams, tribes and patient safety: overcoming barriers to effective teamwork in healthcare.

    PubMed

    Weller, Jennifer; Boyd, Matt; Cumin, David

    2014-03-01

    Modern healthcare is delivered by multidisciplinary, distributed healthcare teams who rely on effective teamwork and communication to ensure effective and safe patient care. However, we know that there is an unacceptable rate of unintended patient harm, and much of this is attributed to failures in communication between health professionals. The extensive literature on teams has identified shared mental models, mutual respect and trust and closed-loop communication as the underpinning conditions required for effective teams. However, a number of challenges exist in the healthcare environment. We explore these in a framework of educational, psychological and organisational challenges to the development of effective healthcare teams. Educational interventions can promote a better understanding of the principles of teamwork, help staff understand each other's roles and perspectives, and help develop specific communication strategies, but may not be sufficient on their own. Psychological barriers, such as professional silos and hierarchies, and organisational barriers such as geographically distributed teams, can increase the chance of communication failures with the potential for patient harm. We propose a seven-step plan to overcome the barriers to effective team communication that incorporates education, psychological and organisational strategies. Recent evidence suggests that improvement in teamwork in healthcare can lead to significant gains in patient safety, measured against efficiency of care, complication rate and mortality. Interventions to improve teamwork in healthcare may be the next major advance in patient outcomes.

  20. College Students Must Overcome Barriers to Use Calorie Labels in Fast-Food Restaurants.

    PubMed

    Stran, Kimberly A; Knol, Linda L; Turner, Lori W; Severt, Kimberly; McCallum, Debra M; Lawrence, Jeannine C

    2016-02-01

    To explore predictors of intention of college students to use calorie labels on fast-food menus and differences in calories ordered after viewing calorie information. Quasi-experimental design. Participants selected a meal from a menu without calorie labels, selected a meal from the same menu with calorie labels, and completed a survey that assessed demographics, dietary habits, Theory of Planned Behavior constructs, and potential barriers to use of calorie labeling. A southern university. Undergraduate university students (n = 97). Predictors of intention to use calorie labels and whether calories selected from the nonlabeled menu differed from the labeled menu. Confirmatory factor analysis, exploratory factor analysis, multiple regression, and paired t tests. Participants ordered significantly fewer calories (P = .02) when selecting from the labeled menu vs the menu without labels. Attitudes (P = .006), subjective norms (P < .001), and perceived behavioral control (P = .01) predicted intention to use calorie information but did not predict a difference in the calories ordered. Hunger (P = .03) and cost (P = .04) were barriers to using the calorie information. If students can overcome barriers, calorie labeling could provide information that college students need to select lower-calorie items at fast-food restaurants. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  1. Cancer cells remodel themselves and vasculature to overcome the endothelial barrier.

    PubMed

    Shenoy, Anitha K; Lu, Jianrong

    2016-10-01

    Metastasis refers to the spread of cancer cells from a primary tumor to distant organs mostly via the bloodstream. During the metastatic process, cancer cells invade blood vessels to enter circulation, and later exit the vasculature at a distant site. Endothelial cells that line blood vessels normally serve as a barrier to the movement of cells into or out of the blood. It is thus critical to understand how metastatic cancer cells overcome the endothelial barrier. Epithelial cancer cells acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT), which enables them to move toward vasculature. Cancer cells also express a variety of adhesion molecules that allow them to attach to vascular endothelium. Finally, cancer cells secrete or induce growth factors and cytokines to actively prompt vascular hyperpermeability that compromises endothelial barrier function and facilitates transmigration of cancer cells through the vascular wall. Elucidation of the mechanisms underlying metastatic dissemination may help develop new anti-metastasis therapeutics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Preparing Dental Students and Residents to Overcome Internal and External Barriers to Evidence-Based Practice.

    PubMed

    Coleman, Brandon G; Johnson, Thomas M; Erley, Kenneth J; Topolski, Richard; Rethman, Michael; Lancaster, Douglas D

    2016-10-01

    In recent years, evidence-based dentistry has become the ideal for research, academia, and clinical practice. However, barriers to implementation are many, including the complexity of interpreting conflicting evidence as well as difficulties in accessing it. Furthermore, many proponents of evidence-based care seem to assume that good evidence consistently exists and that clinicians can and will objectively evaluate data so as to apply the best evidence to individual patients' needs. The authors argue that these shortcomings may mislead many clinicians and that students should be adequately prepared to cope with some of the more complex issues surrounding evidence-based practice. Cognitive biases and heuristics shape every aspect of our lives, including our professional behavior. This article reviews literature from medicine, psychology, and behavioral economics to explore the barriers to implementing evidence-based dentistry. Internal factors include biases that affect clinical decision making: hindsight bias, optimism bias, survivor bias, and blind-spot bias. External factors include publication bias, corporate bias, and lack of transparency that may skew the available evidence in the peer-reviewed literature. Raising awareness of how these biases exert subtle influence on decision making and patient care can lead to a more nuanced discussion of addressing and overcoming barriers to evidence-based practice.

  3. Peptide modules for overcoming barriers of nucleic acids transport to cells.

    PubMed

    Egorova, Anna A; Kiselev, Anton V

    2016-01-01

    Absence of safe and efficient methods of nucleic acids delivery is one of the major issues which limits the development of human gene therapy. Highly efficient viral vectors raise questions due to safety reasons. Among non-viral vectors peptide-based carriers can be considered as good candidates for the development of "artificial viruses"--multifunctional polyplexes that mimic viruses. Suggested strategy to obtain multifunctionality is to combine several peptide modules into one modular carrier. Different kinds of peptide modules are needed for successful overcoming barriers of nucleic acids transport into the cells. Design of such modules and establishment of structure-function relationships are issues of importance to researchers working in the field of nucleic acids delivery.

  4. Building America Guidance for Identifying and Overcoming Code, Standard, and Rating Method Barriers

    SciTech Connect

    Cole, Pamala C.; Halverson, Mark A.

    2013-09-01

    The U.S. Department of Energy’s (DOE) Building America program implemented a new Codes and Standards Innovation (CSI) Team in 2013. The Team’s mission is to assist Building America (BA) research teams and partners in identifying and resolving conflicts between Building America innovations and the various codes and standards that govern the construction of residences. A CSI Roadmap was completed in September, 2013. This guidance document was prepared using the information in the CSI Roadmap to provide BA research teams and partners with specific information and approaches to identifying and overcoming potential barriers to Building America (BA) innovations arising in and/or stemming from codes, standards, and rating methods. For more information on the BA CSI team, please email: CSITeam@pnnl.gov

  5. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption.

    PubMed

    Sheng, Jianyong; Han, Limei; Qin, Jing; Ru, Ge; Li, Ruixiang; Wu, Lihong; Cui, Dongqi; Yang, Pei; He, Yuwei; Wang, Jianxin

    2015-07-22

    Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics.

  6. Overcoming Barriers to Public Engagement through a Multi-Institution Consortium

    NASA Astrophysics Data System (ADS)

    Lambert, K. F.; Weiss, M.; Garlick, S.

    2016-12-01

    A growing body of evidence suggests that public engagement with science (PES) can enhance the relevance and impact of science on society. At the same time, advances in our understanding of public engagement suggest that greater skills, resources, and time horizons are often required to create effective programs. Consequently, despite a proliferation of training programs, many scientists still face the challenge of balancing the demands of public engagement with the requirements of their disciplinary research. Novel institutions are emerging that bring together interdisciplinary networks of principle investigators with PES practitioners to overcome barriers to effective and sustained public engagement in the environmental sciences. We will use the Science Policy Exchange (SPE), a consortium housed at the Harvard Forest, Harvard University, to illustrate how PIs and PES practitioners can collaborate to design public engagement processes, conduct policy-relevant scientific syntheses, and implement science communication strategies. Results from two SPE case studies demonstrate how multi-institutional consortia can help scientists overcome barriers such as lack of knowledge of evidence-based PES approaches, limits on time and funding to implement PES projects, and the need to integrate PES activities with research. The case studies also show how SPE strives to achieve credibility, saliency, and legitimacy in different public policy contexts: (1) engagement between scientists and local stakeholders to develop scenarios of landscape change; and (2) engagement between scientists and policy makers to understand the relationship between power plant emission standards, and air quality, human health and ecosystem function. The presentation will conclude with examples of how SPE programs have led to institutional change (staffing and budget), cultural change (attitudes and expectations of senior leaders), and research change (development of research questions, funding proposals

  7. Cronobacter sakazakii clinical isolates overcome host barriers and evade the immune response.

    PubMed

    Almajed, Faisal S; Forsythe, Stephen J

    2016-01-01

    Cronobacter sakazakii is the most frequently clinically isolated species of the Cronobacter genus. However the virulence factors of C. sakazakii including their ability to overcome host barriers remains poorly studied. In this study, ten clinical isolates of C. sakazakii were assessed for their ability to invade and translocate through human colonic carcinoma epithelial cells (Caco-2) and human brain microvascular endothelial cells (HBMEC). Their ability to avoid phagocytosis in human macrophages U937 and human brain microglial cells was investigated. Additionally, they were tested for serum sensitivity and the presence of the Cronobacter plasminogen activation gene (cpa) gene, which is reported to confer serum resistance. Our data showed that the clinical C. sakazakii strains invaded and translocated through Caco-2 and HBMEC cell lines and some strains showed significantly higher levels of invasion and translocation. Moreover, C. sakazakii was able to persist and even multiply in phagocytic macrophage and microglial cells. All strains, except one, were able to withstand human serum exposure, the single serum sensitive strain was also the only one which did not encode for the cpa gene. These results demonstrate that C. sakazakii clinical isolates are able to overcome host barriers and evade the host immune response indicating their capacity to cause diseases such as necrotizing enterocolitis (NEC) and meningitis. Our data showed for the first time the ability of C. sakazakii clinical isolates to survive and multiply within human microglial cells. Additionally, it was shown that C. sakazakii clinical strains have the capacity to translocate through the Caco-2 and HBMEC cell lines paracellularly.

  8. Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report

    PubMed Central

    Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried OF; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

    2016-01-01

    In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden. PMID:26159464

  9. Overcoming barriers to implementing patient-reported outcomes in an electronic health record: a case report.

    PubMed

    Harle, Christopher A; Listhaus, Alyson; Covarrubias, Constanza M; Schmidt, Siegfried Of; Mackey, Sean; Carek, Peter J; Fillingim, Roger B; Hurley, Robert W

    2016-01-01

    In this case report, the authors describe the implementation of a system for collecting patient-reported outcomes and integrating results in an electronic health record. The objective was to identify lessons learned in overcoming barriers to collecting and integrating patient-reported outcomes in an electronic health record. The authors analyzed qualitative data in 42 documents collected from system development meetings, written feedback from users, and clinical observations with practice staff, providers, and patients. Guided by the Unified Theory on the Adoption and Use of Information Technology, 5 emergent themes were identified. Two barriers emerged: (i) uncertain clinical benefit and (ii) time, work flow, and effort constraints. Three facilitators emerged: (iii) process automation, (iv) usable system interfaces, and (v) collecting patient-reported outcomes for the right patient at the right time. For electronic health record-integrated patient-reported outcomes to succeed as useful clinical tools, system designers must ensure the clinical relevance of the information being collected while minimizing provider, staff, and patient burden.

  10. Creating sustainable local health information exchanges: can barriers to stakeholder participation be overcome?

    PubMed

    Grossman, Joy M; Kushner, Kathryn L; November, Elizabeth A

    2008-02-01

    Local health information exchanges (HIEs) hold the promise of collecting patient clinical data across sites of care to provide more complete and timely information for treatment, as well as supporting quality improvement and reporting, public health activities, and clinical research. Findings from a study of stakeholder perspectives on participation in four HIEs by the Center for Studying Health System Change (HSC) and the National Institute for Health Care Management (NIHCM) Foundation suggest, however, that barriers to achieving data exchange remain high. Concerns about loss of competitive advantage and data misuse impede provider and health plan willingness to contribute patient data. Additionally, uncertainty about who benefits from HIEs is affecting stakeholder willingness to fund the exchanges. The more mature exchanges--Cincinnati-based HealthBridge and the Indiana Health Information Exchange (IHIE)--have achieved some viability by meeting a specific business need--more efficient delivery of hospital test results to physicians. The newer exchanges--CareSpark, serving northeast Tennessee and southwest Virginia, and the Tampa Bay Regional Health Information Organization (RHIO)--have struggled to identify and finance initial services without a similar critical mass of hospital participation. While narrow data exchange efforts that improve transaction efficiency may be a pragmatic first step to overcome barriers to stakeholder participation, expanding HIEs to achieve the broad-based data exchange necessary for quality reporting and pay-for-performance (P4P) activities raises more challenges.

  11. Overcoming Barriers in Kidney Health—Forging a Platform for Innovation

    PubMed Central

    Archdeacon, Patrick; Breyer, Matthew D.; Ibrahim, Tod; Inrig, Jula K.; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y.; Roy-Chaudhury, Prabir; Sloand, James A.; Meyer, Rachel; Smith, Kimberly A.; Snook, Jennifer; West, Melissa

    2016-01-01

    Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology. PMID:27127187

  12. Overcoming Medicaid Reimbursement Barriers to Funding School Nursing Services for Low-Income Children With Asthma.

    PubMed

    Malcarney, Mary-Beth; Horton, Katherine; Seiler, Naomi

    2016-05-01

    School nurses can provide direct services for children with asthma, educate, and reinforce treatment recommendations to children and their families, and coordinate the school-wide response to students' asthma emergencies. Unfortunately, school-based health services today depend on an unreliable patchwork of funding. Limited state and local funds lead to extremely low nurse-to-student ratios, resulting in missed opportunities for prevention and care of asthma and other health conditions. We carried out a nonsystematic review of legal, government, private health foundation, and medical literature. Many health services for asthma and other conditions provided in school settings are services typically covered by Medicaid and the Children's Health Insurance Program (CHIP) when offered in other settings. However, complex reimbursement rules, questionable policy guidance establishing a "free care rule," and other barriers have limited the ability of schools to seek Medicaid/CHIP reimbursement for these services. Recent legal developments may help overcome some of these barriers, and new flexibilities in Medicaid law bring opportunities for increased reimbursement of school-based health services. Policymakers should call on the Centers for Medicare and Medicaid Services to abandon the "free care rule" and issue other guidance that would enable schools to appropriately obtain Medicaid reimbursement for nursing services. © 2016, American School Health Association.

  13. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy.

    PubMed

    Mastorakos, Panagiotis; da Silva, Adriana L; Chisholm, Jane; Song, Eric; Choi, Won Kyu; Boyle, Michael P; Morales, Marcelo M; Hanes, Justin; Suk, Jung Soo

    2015-07-14

    Gene therapy has emerged as an alternative for the treatment of diseases refractory to conventional therapeutics. Synthetic nanoparticle-based gene delivery systems offer highly tunable platforms for the delivery of therapeutic genes. However, the inability to achieve sustained, high-level transgene expression in vivo presents a significant hurdle. The respiratory system, although readily accessible, remains a challenging target, as effective gene therapy mandates colloidal stability in physiological fluids and the ability to overcome biological barriers found in the lung. We formulated highly stable DNA nanoparticles based on state-of-the-art biodegradable polymers, poly(β-amino esters) (PBAEs), possessing a dense corona of polyethylene glycol. We found that these nanoparticles efficiently penetrated the nanoporous and highly adhesive human mucus gel layer that constitutes a primary barrier to reaching the underlying epithelium. We also discovered that these PBAE-based mucus-penetrating DNA nanoparticles (PBAE-MPPs) provided uniform and high-level transgene expression throughout the mouse lungs, superior to several gold standard gene delivery systems. PBAE-MPPs achieved robust transgene expression over at least 4 mo following a single administration, and their transfection efficiency was not attenuated by repeated administrations, underscoring their clinical relevance. Importantly, PBAE-MPPs demonstrated a favorable safety profile with no signs of toxicity following intratracheal administration.

  14. Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

    PubMed

    Linde, Peter G; Archdeacon, Patrick; Breyer, Matthew D; Ibrahim, Tod; Inrig, Jula K; Kewalramani, Reshma; Lee, Celeste Castillo; Neuland, Carolyn Y; Roy-Chaudhury, Prabir; Sloand, James A; Meyer, Rachel; Smith, Kimberly A; Snook, Jennifer; West, Melissa; Falk, Ronald J

    2016-07-01

    Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.

  15. Understanding and Overcoming Barriers to Upper Limb Surgical Reconstruction After Tetraplegia: The Need for Interdisciplinary Collaboration.

    PubMed

    Punj, Vandana; Curtin, Catherine

    2016-06-01

    There are approximately 300,000 persons with spinal cord injury living in the United States, and nearly 60% of these persons have suffered tetraplegia with resultant alterations in body function, activity, and therefore participation. Restoring hand function can improve independence, and various studies have shown that persons with tetraplegia rate restoration of arm and hand function higher than bowel and bladder control, walking, or sexuality. There are conservative options to improve upper limb function in this population (eg, orthoses, neuroprostheses). Surgical interventions are also available, and 70% of surgical patients report satisfaction and improvement in various activities of daily living after surgery to restore arm and hand function. Despite these positive surgical outcomes, <10% of the eligible population of 60% to 70% undergo tendon transfer surgery to restore function. Underutilization of surgical interventions can be explained by population-, provider-, and health care systems-specific barriers. With further education of providers and patients and team building across disciplines these barriers can be overcome, ultimately leading to reduced disability and improved quality of life for persons with tetraplegia.

  16. Electrical, magnetic, photomechanical and cavitational waves to overcome skin barrier for transdermal drug delivery.

    PubMed

    Wong, Tin Wui

    2014-11-10

    Transdermal drug delivery is hindered by the barrier property of the stratum corneum. It limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500Da and melting point of less than 200°C. Active methods such as iontophoresis, electroporation, sonophoresis, magnetophoresis and laser techniques have been investigated for the past decades on their ability, mechanisms and limitations in modifying the skin microenvironment to promote drug diffusion and partition. Microwave, an electromagnetic wave characterized by frequencies range between 300MHz and 300GHz, has recently been reported as the potential skin permeation enhancer. Microwave has received a widespread application in food, engineering and medical sectors. Its potential use to facilitate transdermal drug transport is still in its infancy stage of evaluation. This review provides an overview and update on active methods utilizing electrical, magnetic, photomechanical and cavitational waves to overcome the skin barrier for transdermal drug administration with insights into mechanisms and future perspectives of the latest microwave technique described. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Reaction pathways and free energy barriers for alkaline hydrolysis of insecticide 2-trimethylammonioethyl methylphosphonofluoridate and related organophosphorus compounds: electrostatic and steric effects.

    PubMed

    Xiong, Ying; Zhan, Chang-Guo

    2004-11-26

    substituent R in (RO)CH(3)P(O)F from CH3 to CH2CH2N+(CH3)3 is associated with both the electrostatic and steric effects on the free energy barrier, but the electrostatic effect dominates the substituent shift of the free energy barrier. This helps to better understand why the alkaline hydrolysis of (RO)CH3P(O)F with R = CH2CH2N+(CH3)3 and CH(CH3)CH2N+(CH3)3 is significantly faster than that with R = CH3. The effect of electrostatic interaction also helps to understand why the rate constants for the alkaline hydrolysis of phosphodiesters, such as intramolecular second messenger adenosine 3',5'-phosphate (cAMP), are generally smaller than those for the alkaline hydrolysis of the phosphonofluoridates and related phosphotriesters.

  18. Evidence for Health II: Overcoming barriers to using evidence in policy and practice.

    PubMed

    Andermann, Anne; Pang, Tikki; Newton, John N; Davis, Adrian; Panisset, Ulysses

    2016-03-14

    Even the highest quality evidence will have little impact unless it is incorporated into decision-making for health. It is therefore critical to overcome the many barriers to using evidence in decision-making, including (1) missing the window of opportunity, (2) knowledge gaps and uncertainty, (3) controversy, irrelevant and conflicting evidence, as well as (4) vested interests and conflicts of interest. While this is certainly not a comprehensive list, it covers a number of main themes discussed in the knowledge translation literature on this topic, and better understanding these barriers can help readers of the evidence to be more savvy knowledge users and help researchers overcome challenges to getting their evidence into practice. Thus, the first step in being able to use research evidence for improving population health is ensuring that the evidence is available at the right time and in the right format and language so that knowledge users can take the evidence into consideration alongside a multitude of other factors that also influence decision-making. The sheer volume of scientific publications makes it difficult to find the evidence that can actually help inform decisions for health. Policymakers, especially in low- and middle-income countries, require context-specific evidence to ensure local relevance. Knowledge synthesis and dissemination of policy-relevant local evidence is important, but it is still not enough. There are times when the interpretation of the evidence leads to various controversies and disagreements, which act as barriers to the uptake of evidence. Research evidence can also be influenced and misused for various aims and agendas. It is therefore important to ensure that any new evidence comes from reliable sources and is interpreted in light of the overall body of scientific literature. It is not enough to simply produce evidence, nor even to synthesize and package evidence into a more user-friendly format. Particularly at the policy

  19. 1,4-Bis-Dipp/Mes-1,2,4-Triazolylidenes: Carbene Catalysts That Efficiently Overcome Steric Hindrance in the Redox Esterification of α- and β-Substituted α,β-Enals.

    PubMed

    Yatham, Veera Reddy; Harnying, Wacharee; Kootz, Darius; Neudörfl, Jörg-M; Schlörer, Nils E; Berkessel, Albrecht

    2016-03-02

    As reported by Scheidt and Bode in 2005, sterically nonencumbered α,β-enals are readily converted to saturated esters in the presence of alcohols and N-heterocyclic carbene catalysts, e.g., benzimidazolylidenes or triazolylidenes. However, substituents at the α- or β-position of the α,β-enal substrate are typically not tolerated, thus severely limiting the substrate spectrum. On the basis of our earlier mechanistic studies, a set of N-Mes- or N-Dipp-substituted 1,2,4-triazolium salts were synthesized and evaluated as (pre)catalysts in the redox esterification of various α- or β-substituted enals. In particular the 1,4-bis-Mes/Dipp-1,2,4-triazolylidenes overcome the above limitations and efficiently catalyze the redox esterification of a whole series of α/β-substituted enals hitherto not amenable to NHC-catalyzed transformations. The synthetic value of 1,4-bis-Mes/Dipp-1,2,4-triazolylidenes is further demonstrated by the one-step bicyclization of 10-oxocitral to (racemic) nepetalactone in diastereomerically pure form.

  20. Overcoming Access Barriers for Facility-based Delivery in Low-income Settings: Insights from Bangladesh and Uganda

    PubMed Central

    Rahman, Syed Azizur; Ssengooba, Freddie

    2006-01-01

    Women in both Bangladesh and Uganda face a number of barriers to delivery in professional health facilities, including costs, transportation problems, and sociocultural norms to deliver at home. Some women in both the countries manage to overcome these barriers. This paper reports on a comparative qualitative study investigating how some women and their families were able to use professional delivery services. The study provides insights into the decision-making processes and overcoming access barriers. Husbands were found to be particularly important in Uganda, while, in Bangladesh, a number of individuals could influence care-seeking, including unqualified local healers or traditional birth attendants. In both the settings, cost and transport barriers were often overcome through social networks. Social prohibitions on birth in the health facility did not feature strongly in women's accounts, with several Ugandan women explaining that friends or peers also used facilities, while, in Bangladesh, perceived complications apparently justified the use of professional medical care. Investigating the ways in which some women can overcome common barriers can help inform policy and planning to increase the use of health facilities for child delivery. PMID:17591340

  1. Let's not contribute to disparities: the best methods for teaching clinicians how to overcome language barriers to health care.

    PubMed

    Diamond, Lisa C; Jacobs, Elizabeth A

    2010-05-01

    Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching "Medical Spanish" or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one's own limited non-English language skills.

  2. Transformed Science: Overcoming Barriers of Inequality and Mistrust to Pursue the Agenda of Underrepresented Communities

    NASA Astrophysics Data System (ADS)

    Lyons, Renee

    Educational programs created to provide opportunities for all, in reality often reflect social inequalities. Such is the case for Public Participation in Scientific Research (PPSR) Projects. PPSR projects have been proposed as an effective way to engage more diverse audiences in science, yet the demographics of PPSR participants do not correspond with the demographic makeup of the United States. The field of PPSR as a whole has struggled to recruit low SES and underrepresented populations to participate in project research efforts. This research study explores factors, which may be affecting an underrepresented community's willingness to engage in scientific research and provides advice from PPSR project leaders in the field, who have been able to engage underrepresented communities in scientific research, on how to overcome these barriers. Finally the study investigates the theoretical construct of a Third Space within a PPSR project. The research-based recommendations for PPSR projects desiring to initiate and sustain research partnerships with underrepresented communities well align with the theoretical construct of a Third Space. This study examines a specific scientific research partnership between an underrepresented community and scientific researchers to examine if and to what extent a Third Space was created. Using qualitative methods to understand interactions and processes involved in initiating and sustaining a scientific research partnership, this study provides advice on how PPSR research partnerships can engage underrepresented communities in scientific research. Study results show inequality and mistrust of powerful institutions stood as participation barriers for underrepresented community members. Despite these barriers PPSR project leaders recommend barriers can be confronted by open dialogue with communities about the abuse and alienation they have faced, by signaling respect for the community, and by entering the community through someone the

  3. Reassortment and mutation of the avian influenza virus polymerase PA subunit overcome species barriers.

    PubMed

    Mehle, Andrew; Dugan, Vivien G; Taubenberger, Jeffery K; Doudna, Jennifer A

    2012-02-01

    The emergence of new pandemic influenza A viruses requires overcoming barriers to cross-species transmission as viruses move from animal reservoirs into humans. This complicated process is driven by both individual gene mutations and genome reassortments. The viral polymerase complex, composed of the proteins PB1, PB2, and PA, is a major factor controlling host adaptation, and reassortment events involving polymerase gene segments occurred with past pandemic viruses. Here we investigate the ability of polymerase reassortment to restore the activity of an avian influenza virus polymerase that is normally impaired in human cells. Our data show that the substitution of human-origin PA subunits into an avian influenza virus polymerase alleviates restriction in human cells and increases polymerase activity in vitro. Reassortants with 2009 pandemic H1N1 PA proteins were the most active. Mutational analyses demonstrated that the majority of the enhancing activity in human PA results from a threonine-to-serine change at residue 552. Reassortant viruses with avian polymerases and human PA subunits, or simply the T552S mutation, displayed faster replication kinetics in culture and increased pathogenicity in mice compared to those containing a wholly avian polymerase complex. Thus, the acquisition of a human PA subunit, or the signature T552S mutation, is a potential mechanism to overcome the species-specific restriction of avian polymerases and increase virus replication. Our data suggest that the human, avian, swine, and 2009 H1N1-like viruses that are currently cocirculating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity.

  4. Lung Gene Therapy with Highly Compacted DNA Nanoparticles that Overcome the Mucus Barrier

    PubMed Central

    Suk, Jung Soo; Kim, Anthony J.; Trehan, Kanika; Schneider, Craig S.; Cebotaru, Liudmila; Woodward, Owen M.; Boylan, Nicholas J.; Boyle, Michael P.; Lai, Samuel K.; Guggino, William B.; Hanes, Justin

    2014-01-01

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  5. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier.

    PubMed

    Suk, Jung Soo; Kim, Anthony J; Trehan, Kanika; Schneider, Craig S; Cebotaru, Liudmila; Woodward, Owen M; Boylan, Nicholas J; Boyle, Michael P; Lai, Samuel K; Guggino, William B; Hanes, Justin

    2014-03-28

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in the mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Nano-carrier systems: Strategies to overcome the mucus gel barrier.

    PubMed

    Dünnhaupt, S; Kammona, O; Waldner, C; Kiparissides, C; Bernkop-Schnürch, A

    2015-10-01

    The present review provides an overview of nanotechnology-based strategies to overcome various mucus gel barriers including the intestinal, nasal, ocular, vaginal, buccal and pulmonary mucus layer without destroying them. It focuses on the one hand on strategies to improve the mucus permeation behavior of particles and on the other hand on systems avoiding the back-diffusion of particles out of the mucus gel layer. Nanocarriers with improved mucus permeation behavior either exhibit a high density of positive and negative charges, bearing mucolytic enzymes such as papain and bromelain on their surface or display a slippery surface due to PEG-ylation. Furthermore, self-nanoemulsifying-drug-delivery-systems (SNEDDS) turned out to exhibit comparatively high mucus permeating properties. Strategies in order to avoid back-diffusion are based on thiolated polymers reacting to a higher extent with cysteine subunits of the mucus at pH 7 in deeper mucus regions than at pH 5 being prevalent in luminal mucus regions of the intestinal and vaginal mucosa. Furthermore, particles changing their zeta potential from negative to positive once they have reached the epithelium seem to be promising carriers. The summarized knowledge should provide a good starting point for further developments in this field. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Overcoming barriers to hepatitis B immunisation by a dedicated hepatitis B immunisation service

    PubMed Central

    Larcher, V; Bourne, J; Aitken, C; Jeffries, D; Hodes, D; SLOAN, D.; RAMSAY, M.; GOLDBERG, D.; BRAMLEY, C.

    2001-01-01

    AIMS—To determine the effectiveness of a selective hospital based hepatitis B immunisation programme and the barriers to be overcome in obtaining a successful outcome.
METHODS—Retrospective case note review of 265 infants born over a five year period to hepatitis B carrier mothers at a university affiliated hospital in Hackney, London.
RESULTS—A total of 242 infants (91%) were fully vaccinated; 217 (82%) had serology; 31 required booster doses. Percentages failing to reach second, third vaccinations, and serology on schedule rose exponentially (7%, 18%, 33% respectively). Mobility was high (25%) and significantly affected outcome. A total of 95% Hackney resident babies were fully vaccinated compared with 78% non-residents. Uptake of routine immunisations was higher in Hackney residents than non-residents and greater in those who were eligible for hepatitis B vaccine. Name changes occurred in 35%. Translation requirements were high (85% for Turkish, Vietnamese, and Asian families). Requirements for specific postnatal counselling of mothers and hepatology referral fell significantly during the course of the study. Only seven of 22 babies born in 1995 in Tower Hamlets compared with 53 of 58 Hackney babies received a full vaccination course in non-hospital based primary care.
CONCLUSION—In inner city areas with high prevalence of hepatitis B carriage, mobility, and diverse ethnicity, a dedicated centralised immunisation service can be highly effective, provided that adequate support services (translation, counselling, and parental referral) are available.
 PMID:11159283

  8. Translating Research to Practice: Overcoming Barriers to Implementing Effective Off-Campus Party Intervention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on overcoming barriers in implementing effective off-campus party intervention. This issue contains the following articles: (1) Confronting the Problems Associated With Off-Campus Parties With Evidence-Based Strategies (John D. Clapp); (2) Overview of Research on Effective Off-Campus Party…

  9. Helping Our Most Vulnerable Families Overcome Barriers to Work and Achieve Financial Success. KIDS COUNT 2005 Essay

    ERIC Educational Resources Information Center

    Annie E. Casey Foundation, 2005

    2005-01-01

    This essay, taken from the 2005 KIDS COUNT Data Book, examines four employment barriers that policymakers and others consider among the most difficult to overcome: substance abuse, domestic violence, a history of incarceration, and depression. These burdens can diminish a person's motivation and ability to find work. Furthermore, they can make it…

  10. Overcoming Relationship-Initiation Barriers: The Impact of a Computer-Dating System on Sex Role, Shyness, and Appearance Inhibitions.

    ERIC Educational Resources Information Center

    Scharlott, Bradford W.; Christ, William G.

    1995-01-01

    A survey of the users of an online computer-mediated matchmaking service showed that their communication patterns and objectives varied by their sex, shyness level, and appearance. Intrinsic aspects of this system helped some users overcome relationship-initiation barriers rooted in sex role, shyness, and appearance inhibitions. (Author)

  11. Overcoming Relationship-Initiation Barriers: The Impact of a Computer-Dating System on Sex Role, Shyness, and Appearance Inhibitions.

    ERIC Educational Resources Information Center

    Scharlott, Bradford W.; Christ, William G.

    1995-01-01

    A survey of the users of an online computer-mediated matchmaking service showed that their communication patterns and objectives varied by their sex, shyness level, and appearance. Intrinsic aspects of this system helped some users overcome relationship-initiation barriers rooted in sex role, shyness, and appearance inhibitions. (Author)

  12. Overcoming Barriers; Enabling Learners: Planning, Designing and Delivering the Full-Time FE Curriculum in Scotland's Colleges

    ERIC Educational Resources Information Center

    Her Majesty's Inspectorate of Education, 2006

    2006-01-01

    The further education (FE) curriculum in Scotland's colleges aims to enable people to develop skills and capacities which will improve the quality of their working, personal, family and community life. To achieve this aim people need assistance to overcome barriers constraining their confidence and ability to take part in learning situations and…

  13. All Health Plans Need CLAMS: Culturally and Linguistically Appropriate Materials for Diverse Populations Can Overcome Language Barriers to Effective Treatment.

    ERIC Educational Resources Information Center

    Smith, Sandra; Gonzales, Virginia

    2000-01-01

    CLAMs are "Culturally and Linguistically Appropriate Materials" designed for diverse populations to help them overcome language barriers to effective treatment. The demographic shift underway in the United States is making the country more linguistically diverse. Health plans need to accommodate this shift, because without information patients…

  14. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye - Part I - Barriers and determining factors in ocular delivery.

    PubMed

    Sánchez-López, E; Espina, M; Doktorovova, S; Souto, E B; García, M L

    2017-01-01

    Ocular drug delivery is still a challenge for researchers in the field of pharmaceutical technology due to anatomical and physiological eye characteristics. The tissue barriers (such as cornea, conjunctiva, blood aqueous barrier, and blood-retinal barrier) limit the access of drugs to their targets. Taking into account the short retention time in the precorneal area of classical ocular dosage forms (e.g. solutions, suspensions or ointments) which are rapidly eliminated by tears and eyelid movement, only less than five percent of the administered drug attains intraocular structures. With the aim to overcome ocular barriers, drug delivery systems, able to increase ocular bioavailability reducing side effects, are recognized as promising alternative. In this review, the main barriers and strategies to increase drug transport in ocular delivery are comprehensively discussed, highlighting the factors involved in ocular transport of SLN and NLC.

  15. Tuning PEGylation of mixed micelles to overcome intracellular and systemic siRNA delivery barriers

    PubMed Central

    Miteva, Martina; Kirkbride, Kellye C.; Kilchrist, Kameron V.; Werfel, Thomas A.; Li, Hongmei; Nelson, Christopher E.; Gupta, Mukesh K.; Giorgio, Todd D.; Duvall, Craig L.

    2017-01-01

    A series of endosomolytic mixed micelles was synthesized from two diblock polymers, poly[ethylene glycol-b-(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate)] (PEG-b-pDPB) and poly[dimethylaminoethyl methacrylate-b-(dimethylaminoethyl methacrylate-co-propylacrylic acid-co-butyl methacrylate)] (pD-b-pDPB), and used to determine the impact of both surface PEG density and PEG molecular weight on overcoming both intracellular and systemic siRNA delivery barriers. As expected, the percent PEG composition and PEG molecular weight in the corona had an inverse relationship with mixed micelle zeta potential and rate of cellular internalization. Although mixed micelles were internalized more slowly, they generally produced similar gene silencing bioactivity (~80% or greater) in MDA-MB-231 breast cancer cells as the micelles containing no PEG (100D/no PEG). The mechanistic explanation for the potent bioactivity of the promising 50 mol% PEG-b-DPB/50 mol% pD-b-pDPB (50D) mixed micelle formulation, despite its relatively low rate of cellular internalization, was further investigated as a function of PEG molecular weight (5 k, 10 k, or 20 k PEG). Results indicated that, although larger molecular weight PEG decreased cellular internalization, it improved cytoplasmic bioavailability due to increased intracellular unpackaging (quantitatively measured via FRET) and endosomal release. When delivered intravenously in vivo, 50D mixed micelles with a larger molecular weight PEG in the corona also demonstrated significantly improved blood circulation half-life (17.8 min for 20 k PEG micelles vs. 4.6 min for 5 kDa PEG micelles) and a 4-fold decrease in lung accumulation. These studies provide new mechanistic insights into the functional effects of mixed micelle-based approaches to nanocarrier surface PEGylation. Furthermore, the ideal mixed micelle formulation identified (50D/20 k PEG) demonstrated desirable intracellular and systemic pharmacokinetics and thus

  16. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier.

    PubMed

    Pereira de Sousa, Irene; Cattoz, Beatrice; Wilcox, Matthew D; Griffiths, Peter C; Dalgliesh, Robert; Rogers, Sarah; Bernkop-Schnürch, Andreas

    2015-11-01

    The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems.

  17. Policy barriers to health care access fuel discriminatory treatment: the role of Promotoras in overcoming malos tratos.

    PubMed

    Pacheco, Tania L; Ramirez, Mariana A; Capitman, John A

    2012-01-01

    This article demonstrates that policy barriers resulting in access to health care inequities were significantly decreased by 2 Promotora interventions for 416 legal and undocumented Latino immigrants in the California Central Valley. Promotoras conducted baseline/follow-up assessments and referrals/phone-calls/visits during a 3-month period. In-depth interviews with Promotoras and a policy analysis on policy-driven access programs were carried out. Access to care was significantly increased between legal and undocumented immigrant from baseline to follow-up. Systemic barriers to access (malos tratos) reflected on personal barriers such as affordability of care. Promotoras help participants overcome barriers but do not change the policies determining access and procedures.

  18. Overcoming Barriers to Implementation of Evidence-Based Practice Concepts in Athletic Training Education: Perceptions of Select Educators

    PubMed Central

    Manspeaker, Sarah; Van Lunen, Bonnie

    2011-01-01

    Context: The need to include evidence-based practice (EBP) concepts in entry-level athletic training education is evident as the profession transitions toward using evidence to inform clinical decision making. Objective: To evaluate athletic training educators' experience with implementation of EBP concepts in Commission on Accreditation of Athletic Training Education (CAATE)-accredited entry-level athletic training education programs in reference to educational barriers and strategies for overcoming these barriers. Design: Qualitative interviews of emergent design with grounded theory. Setting: Undergraduate CAATE-accredited athletic training education programs. Patients or Other Participants: Eleven educators (3 men, 8 women). The average number of years teaching was 14.73 ± 7.06. Data Collection and Analysis: Interviews were conducted to evaluate perceived barriers and strategies for overcoming these barriers to implementation of evidence-based concepts in the curriculum. Interviews were explored qualitatively through open and axial coding. Established themes and categories were triangulated and member checked to determine trustworthiness. Results: Educators identified 3 categories of need for EBP instruction: respect for the athletic training profession, use of EBP as part of the decision-making toolbox, and third-party reimbursement. Barriers to incorporating EBP concepts included time, role strain, knowledge, and the gap between clinical and educational practices. Suggested strategies for surmounting barriers included identifying a starting point for inclusion and approaching inclusion from a faculty perspective. Conclusions: Educators must transition toward instruction of EBP, regardless of barriers present in their academic programs, in order to maintain progress with other health professions' clinical practices and educational standards. Because today's students are tomorrow's clinicians, we need to include EBP concepts in entry-level education to promote

  19. Overcoming barriers to implementation of evidence-based practice concepts in athletic training education: perceptions of select educators.

    PubMed

    Manspeaker, Sarah; Van Lunen, Bonnie

    2011-01-01

    The need to include evidence-based practice (EBP) concepts in entry-level athletic training education is evident as the profession transitions toward using evidence to inform clinical decision making. To evaluate athletic training educators' experience with implementation of EBP concepts in Commission on Accreditation of Athletic Training Education (CAATE)-accredited entry-level athletic training education programs in reference to educational barriers and strategies for overcoming these barriers. Qualitative interviews of emergent design with grounded theory. Undergraduate CAATE-accredited athletic training education programs. Eleven educators (3 men, 8 women). The average number of years teaching was 14.73 ± 7.06. Interviews were conducted to evaluate perceived barriers and strategies for overcoming these barriers to implementation of evidence-based concepts in the curriculum. Interviews were explored qualitatively through open and axial coding. Established themes and categories were triangulated and member checked to determine trustworthiness. Educators identified 3 categories of need for EBP instruction: respect for the athletic training profession, use of EBP as part of the decision-making toolbox, and third-party reimbursement. Barriers to incorporating EBP concepts included time, role strain, knowledge, and the gap between clinical and educational practices. Suggested strategies for surmounting barriers included identifying a starting point for inclusion and approaching inclusion from a faculty perspective. Educators must transition toward instruction of EBP, regardless of barriers present in their academic programs, in order to maintain progress with other health professions' clinical practices and educational standards. Because today's students are tomorrow's clinicians, we need to include EBP concepts in entry-level education to promote critical thinking, inspire potential research interest, and further develop the available body of knowledge in our

  20. Overcoming hybridization barriers by the secretion of the maize pollen tube attractant ZmEA1 from Arabidopsis ovules.

    PubMed

    Márton, Mihaela L; Fastner, Astrid; Uebler, Susanne; Dresselhaus, Thomas

    2012-07-10

    A major goal of plant reproduction research is to understand and overcome hybridization barriers so that the gene pool of crop plants can be increased and improved upon. After successful pollen germination on a receptive stigma, the nonmotile sperm cells of flowering plants are transported via the pollen tube (PT) to the egg apparatus for the achievement of double fertilization. The PT path is controlled by various hybridization mechanisms probably involving a larger number of species-specific molecular interactions. The egg-apparatus-secreted polymorphic peptides ZmEA1 in maize and LURE1 and LURE2 in Torenia fournieri as well as TcCRP1 in T. concolor were shown to be required for micropylar PT guidance, the last step of the PT journey. We report here that ZmEA1 attracts maize PTs in vitro and arrests their growth at higher concentrations. Furthermore, it binds to the subapical region of maize PT tips in a species-preferential manner. To overcome hybridization barriers at the level of gametophytic PT guidance, we expressed ZmEA1 in Arabidopsis synergid cells. Secreted ZmEA1 enabled Arabidopsis ovules to guide maize PT in vitro in a species-preferential manner to the micropylar opening of the ovule. These results demonstrate that the egg-apparatus-controlled reproductive-isolation barrier of PT guidance can be overcome even between unrelated plant families.

  1. Implementing an intravenous insulin protocol in your practice: practical advice to overcome clinical, administrative, and financial barriers.

    PubMed

    Kelly, Janet L; Hirsch, Irl B; Furnary, Anthony P

    2006-01-01

    Diabetes mellitus is the fourth most common comorbid condition among hospitalized patients, and 30% of patients undergoing open-heart surgery have diabetes. The link between hyperglycemia and poor outcome has been well described, and large clinical trials have shown that aggressive control of blood glucose with an insulin infusion can improve these outcomes. The barriers to implementing an insulin infusion protocol are numerous, despite the fact that doing so is paramount to clinical success. Barriers include safety concerns, such as fear of hypoglycemia, insufficient nursing staff to patient ratios, lack of administrative and physician support, various system and procedural issues, and resistance to change. Key steps to overcome the barriers include building support with multidisciplinary champions, involving key staff, educating staff, and administrators of the clinical and economic benefits of improving glycemic control, setting realistic goals, selecting a validated insulin infusion protocol, and internally marketing the success of the protocol.

  2. Simulations and Games: Overcoming the Barriers to Their Use in Higher Education

    ERIC Educational Resources Information Center

    Moizer, Jonathan; Lean, Jonathan; Towler, Michael; Abbey, Caroline

    2009-01-01

    Based on a categorization of simulation and gaming barriers developed in a previous study, this work seeks to explore in greater depth the composition and nature of these obstacles. It examines the interrelationships between the barriers and the impact of other contextual factors in the pedagogic environment. A series of in-depth interviews were…

  3. Energy management action plan: Developing a strategy for overcoming institutional barriers to municipal energy conservation

    SciTech Connect

    Not Available

    1992-12-31

    Energy offices working to improve efficiency of local government facilities face not only technical tasks, but institutional barriers, such as budget structures that do not reward efficiency, a low awareness of energy issues, and purchasing procedures based only on minimizing initial cost. The bureau, in working to remove such barriers in San Francisco, has identified 37 institutional barriers in areas such as operations & maintenance, purchasing, and facility design; these barriers were then reorganized into three groupings-- policy & attitudes, budget & incentives, and awareness & information-- and mapped. This map shows that the barriers mutually reinforce each other, and that a holistic approach is required for permanent change. The city`s recreation & parks department was used as a model department, and information about facility energy use was compiled into a departmental energy review. Staff interviews showed how barriers affect conservation. The bureau then generated ideas for projects to remove specific barriers and rated them according to potential impact and the resources required to implement them. Four of the six projects selected focused on maintenance staff: a cost- sharing lighting retrofit program, a boiler efficiency program, a departmental energy tracking system, and a budgetary incentive program for conservation. The other two projects are city-wide: promotion of a new term contract supplying energy-efficient light materials, and publication/distribution of ENERGY NEWS newsletter. A general methodology, the EMAP Strategy Guide, has been created to assist other energy offices in developing EMAPs.

  4. A review of multifunctional nanoemulsion systems to overcome oral and CNS drug delivery barriers.

    PubMed

    Ganta, Srinivas; Deshpande, Dipti; Korde, Anisha; Amiji, Mansoor

    2010-10-01

    The oral and central nervous systems (CNS) present a unique set of barriers to the delivery of important diagnostic and therapeutic agents. Extensive research over the past few years has enabled a better understanding of these physical and biological barriers based on tight cellular junctions and expression of active transporters and metabolizing enzymes at the luminal surfaces of the gastrointestinal (GI) tract and the blood-brain barrier (BBB). This review focuses on the recent understanding of transport across the GI tract and BBB and the development of nanotechnology-based delivery strategies that can enhance bioavailability of drugs. Multifunctional lipid nanosystems, such as oil-in-water nanoemulsions, that integrate enhancement in permeability, tissue and cell targeting, imaging, and therapeutic functions are especially promising. Based on strategic choice of edible oils, surfactants and additional surface modifiers, and different types of payloads, rationale design of multifunctional nanoemulsions can serve as a safe and effective delivery vehicle across oral and CNS barriers.

  5. Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes.

    PubMed

    Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

    2010-03-17

    In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements.1. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.2. We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies.Twelve studies provided enough data to be included in the quantitative analysis. A meta-regression model was fitted

  6. Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

    PubMed Central

    Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

    2014-01-01

    Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided

  7. Ground-Source Heat Pumps. Overview of Market Status, Barriers to Adoption, and Options for Overcoming Barriers

    SciTech Connect

    Goetzler, William; Zogg, Robert; Lisle, Heather; Burgos, Javier

    2009-02-03

    February 2009 final report submitted to DOE by Navigant Consulting, Inc. This report summarizes the status of ground-source heat pump (GSHP) technology and market penetration globally, estimates the energy saving potential of GSHPs in the U.S., identifies key market barriers that are inhibiting wider market adoption of GSHPs, and recommends initiatives that can be implemented or facilitated by the DOE to accelerate market adoption.

  8. Barriers that practitioners face when initiating insulin therapy in general practice settings and how they can be overcome

    PubMed Central

    Bin rsheed, Abdulaziz; Chenoweth, Ian

    2017-01-01

    AIM To explore primary care physicians’ perspectives on possible barriers to the use of insulin. METHODS This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight electronic databases were searched (between January 1, 1994 and August 31, 2014) for relevant studies. A search for grey literature and a review of the references in the retrieved studies were also conducted. Studies that focused on healthcare providers’ perspectives on possible barriers to insulin initiation with type 2 diabetic patients were included, as well as articles suggesting solutions for these barriers. Review articles and studies that only considered patients’ perspectives were excluded. RESULTS A total of 19 studies met the inclusion criteria and were therefore included in this study: 10 of these studies used qualitative methods, 8 used quantitative methods and 1 used mixed methods. Studies included a range of different health care settings. The findings are reported under four broad categories: The perceptions of primary care physicians about the barriers to initiate insulin therapy for type 2 diabetes patients, how primary care physicians assess patients prior to initiating insulin, professional roles and possible solutions to overcome these barriers. The barriers described were many and covered doctor, patient, system and technological aspects. Interventions that focused on doctor training and support, or IT-based decision support were few, and did not result in significant improvement. CONCLUSION Primary care physicians’ known delay in insulin initiation is multifactorial. Published reports of attempts to find solutions for these barriers were limited in number. PMID:28138362

  9. Overcoming the perceived barriers to health care access among single mothers in coastal Kenya.

    PubMed

    Cohen, J J; Blevins, M; Mapenzi, A; Reppart, L; Reppart, J; Mainthia, R; Wester, C W

    2014-02-01

    This study assesses the effects of a comprehensive empowerment intervention on barriers to health care access for single mothers in coastal Kenya. We surveyed 41 single mothers who completed a pilot empowerment program and 60 single mothers who had not yet initiated the program. Comparisons were made using bivariate tests of association and logistic regression. Women in the pilot program were less likely to report transportation costs (OR = 0.26; 95 % CI [0.11-0.59], p = 0.001) and hospital fees (OR = 0.22 [0.10-0.49], p < 0.001) as barriers. Pilot program mothers were more likely to visit a public hospital for their children (OR = 4.38; [1.58-12.1], p = 0.004) and self (OR = 4.70; [1.54-14.4], p = 0.007) when ill. Empowerment programs can alleviate perceived barriers to health care among vulnerable populations.

  10. Overcoming the barrier of narrative adherence in conflicts through awareness of the psychological bias of naïve realism.

    PubMed

    Nasie, Meytal; Bar-Tal, Daniel; Pliskin, Ruthie; Nahhas, Eman; Halperin, Eran

    2014-11-01

    One significant socio-psychological barrier for peaceful resolution of conflicts is each party's adherence to its own collective narrative. We hypothesized that raising awareness to the psychological bias of naïve realism and its identification in oneself would provide a path to overcoming this barrier, thus increasing openness to the adversary's narrative. We conducted three experimental studies in the context of the Israeli-Palestinian conflict. Studies 1 and 2, conducted among Jewish Israelis and Palestinian Israelis, respectively, revealed that participants with hawkish political ideology reported greater openness to the adversary's narrative when they were made aware of naïve realism bias. Study 3 revealed that hawkish participants at the baseline adhered to the ingroup narrative and resisted the adversary's narrative more than dovish participants. They were also more able to identify the bias in themselves upon learning about it. This identification may explain why the manipulation led to bias correction only among hawkish participants.

  11. Writing for Publication: An Intervention to Overcome Barriers to Scholarly Writing

    ERIC Educational Resources Information Center

    Kapp, C. A.; Albertyn, R. M.; Frick, B. L.

    2011-01-01

    Academics are actively encouraged to disseminate new knowledge to the scientific community by publishing in scholarly journals. External and internal barriers to writing, however, prevent many authors from writing for publication. This article gives an account of an intervention to provide hands-on coaching to inexperienced academic authors.…

  12. Strategies for Overcoming Barriers to Training and Education for Canadians with Disabilities. Lessons in Learning

    ERIC Educational Resources Information Center

    Canadian Council on Learning, 2009

    2009-01-01

    If stronger skills and more education are key to greater labour force participation, then it is important to identify critical barriers to education and training for Canadians with disabilities. In 2008, the Canadian Council on Learning's Adult Learning Knowledge Centre funded a "Community Outreach Initiative for Learner's with…

  13. Supporting Instructors in Overcoming Self-Efficacy and Background Barriers to Adoption

    ERIC Educational Resources Information Center

    Reid, Pat

    2017-01-01

    Most academic technology areas of higher education institutes do not feel faculty technology adoption is adequate (Hartman (EDUCAUSE Rev 43(6), 2008)). Among the barriers to instructional technology adoption are faculty self-efficacy and background. Self-efficacy encompasses the faculty member's belief or confidence in his ability to succeed.…

  14. Achieving Cross-Domain Synergy: Overcoming Service Barriers to Joint Force 2020

    DTIC Science & Technology

    2014-06-13

    solution such as the cultural analysis performed during mergers, acquisitions, and joint ventures may be necessary to mitigate individual service...these barriers, it was discovered that a corporate solution such as the cultural analysis performed during mergers, acquisitions, and joint ventures...7 Lewins Force Field Analysis

  15. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    ERIC Educational Resources Information Center

    Justice, Laura M.; Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their…

  16. At-Risk Students Defy the Odds: Overcoming Barriers to Educational Success.

    ERIC Educational Resources Information Center

    Aronson, Rosa

    The phenomenon of educational resilience in at-risk students involves complex questions and answers. Seven people were interviewed whose lives are chronicled in the context of surviving and achieving despite significant barriers to success in life. They encountered common hindrances arising from poverty, racial and ethnic identity, isolation,…

  17. Learning from the Best: Overcoming Barriers to Reforms-Based Elementary Science Teaching

    ERIC Educational Resources Information Center

    Banchi, Heather May

    2009-01-01

    This study explored the characteristics of elementary science teachers who employ reforms-based practices. Particular attention was paid to the consistency of teachers' practices and their beliefs, the impact of professional development experiences on practices, and how teachers mitigated barriers to reforms-based instruction. Understanding how…

  18. Overcoming Barriers to the Sexual Expression of Women with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Stinson, Jennifer; Christian, LeeAnn; Dotson, Lori Ann

    2002-01-01

    This article discusses barriers to sexual fulfillment faced by women with developmental disabilities, including: access to gynecological healthcare, limited choices regarding reproductive issues, lack of sex education, and prevailing negative stereotypes that affect the way women are viewed by others and the way they view themselves.…

  19. Supporting Instructors in Overcoming Self-Efficacy and Background Barriers to Adoption

    ERIC Educational Resources Information Center

    Reid, Pat

    2017-01-01

    Most academic technology areas of higher education institutes do not feel faculty technology adoption is adequate (Hartman (EDUCAUSE Rev 43(6), 2008)). Among the barriers to instructional technology adoption are faculty self-efficacy and background. Self-efficacy encompasses the faculty member's belief or confidence in his ability to succeed.…

  20. Designing Caregiver-Implemented Shared-Reading Interventions to Overcome Implementation Barriers

    ERIC Educational Resources Information Center

    Justice, Laura M.; Logan, Jessica R.; Damschroder, Laura

    2015-01-01

    Purpose: This study presents an application of the theoretical domains framework (TDF; Michie et al., 2005), an integrative framework drawing on behavior-change theories, to speech-language pathology. Methods: A multistep procedure was used to identify barriers affecting caregivers' implementation of shared-reading interventions with their…

  1. Overcoming Barriers to the Sexual Expression of Women with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Stinson, Jennifer; Christian, LeeAnn; Dotson, Lori Ann

    2002-01-01

    This article discusses barriers to sexual fulfillment faced by women with developmental disabilities, including: access to gynecological healthcare, limited choices regarding reproductive issues, lack of sex education, and prevailing negative stereotypes that affect the way women are viewed by others and the way they view themselves.…

  2. Overcoming Barriers to the Market Access of Biosimilars in the European Union: The Case of Biosimilar Monoclonal Antibodies

    PubMed Central

    Moorkens, Evelien; Jonker-Exler, Clara; Huys, Isabelle; Declerck, Paul; Simoens, Steven; Vulto, Arnold G.

    2016-01-01

    Background: In 2014, six of the top ten blockbuster medicines were monoclonal antibodies. This multibillion-dollar market with expiring patents is the main driver for the development of biosimilar mAbs. With the ever-increasing cost of healthcare and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing costs for medication and increasing patient access to treatment. Objectives: The aim of this study is to identify and describe the barriers to market access of biosimilar mAbs in the European Union and to analyze how these barriers could be overcome. Methods: A narrative literature review was carried out using the databases PubMed, Embase, and EconLit. Studies were published in English or Dutch. Additionally, the reference list of the articles was checked for relevant studies. Articles and conference papers known to the authors were included as well. Articles were also identified by searching on the website of the Generics and Biosimilars Initiative (GaBI) journal. Results: Six barriers were identified based on available literature: The manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator's reach. These six barriers are presented as a possible framework to study the market access of biosimilar mAbs. Based on the literature search, recommendations can be made to overcome these barriers: (i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing (ii) gain experience with the regulatory process and establish alignment between stakeholders (iii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU (iv) create demand-side policies, disseminate objective information (v) change attitude toward biosimilar switching/substitution, starting with physician, and patient

  3. Overcoming Barriers to the Market Access of Biosimilars in the European Union: The Case of Biosimilar Monoclonal Antibodies.

    PubMed

    Moorkens, Evelien; Jonker-Exler, Clara; Huys, Isabelle; Declerck, Paul; Simoens, Steven; Vulto, Arnold G

    2016-01-01

    In 2014, six of the top ten blockbuster medicines were monoclonal antibodies. This multibillion-dollar market with expiring patents is the main driver for the development of biosimilar mAbs. With the ever-increasing cost of healthcare and the economic pressure to reduce or sustain healthcare expenses, biosimilars could be instrumental in reducing costs for medication and increasing patient access to treatment. The aim of this study is to identify and describe the barriers to market access of biosimilar mAbs in the European Union and to analyze how these barriers could be overcome. A narrative literature review was carried out using the databases PubMed, Embase, and EconLit. Studies were published in English or Dutch. Additionally, the reference list of the articles was checked for relevant studies. Articles and conference papers known to the authors were included as well. Articles were also identified by searching on the website of the Generics and Biosimilars Initiative (GaBI) journal. Six barriers were identified based on available literature: The manufacturing process, the regulatory process, intellectual property rights, lack of incentive, the impossibility of substitution, and the innovator's reach. These six barriers are presented as a possible framework to study the market access of biosimilar mAbs. Based on the literature search, recommendations can be made to overcome these barriers: (i) invest initially in advanced production processes with the help of single-use technology, experience or outsourcing (ii) gain experience with the regulatory process and establish alignment between stakeholders (iii) limit patent litigation, eliminate evergreening benefits, build out further the unitary patent and unified patent litigation system within the EU (iv) create demand-side policies, disseminate objective information (v) change attitude toward biosimilar switching/substitution, starting with physician, and patient education (vi) differentiate the biosimilar by

  4. Overcoming Barriers in Unhealthy Settings: A Phenomenological Study of Healthy Truck Drivers.

    PubMed

    Lemke, Michael K; Meissen, Gregory J; Apostolopoulos, Yorghos

    2016-01-01

    We investigated the phenomenon of sustained health-supportive behaviors among long-haul commercial truck drivers, who belong to an occupational segment with extreme health disparities. With a focus on setting-level factors, this study sought to discover ways in which individuals exhibit resiliency while immersed in endemically obesogenic environments, as well as understand setting-level barriers to engaging in health-supportive behaviors. Using a transcendental phenomenological research design, 12 long-haul truck drivers who met screening criteria were selected using purposeful maximum sampling. Seven broad themes were identified: access to health resources, barriers to health behaviors, recommended alternative settings, constituents of health behavior, motivation for health behaviors, attitude toward health behaviors, and trucking culture. We suggest applying ecological theories of health behavior and settings approaches to improve driver health. We also propose the Integrative and Dynamic Healthy Commercial Driving (IDHCD) paradigm, grounded in complexity science, as a new theoretical framework for improving driver health outcomes.

  5. Understanding and overcoming barriers to substance abuse treatment access for people with mental retardation.

    PubMed

    Slayter, Elspeth M

    2008-01-01

    People with mental retardation have experienced increasing levels of freedom and access to community living over the past 40 years. This has included access to alcohol, illicit drugs and the potential for developing substance abuse and related problems. The manner in which people with mental retardation have handled this access has been recognized since the de institutionalization era began. Despite this recognition, documented barriers to accessing substance abuse treatment for people with mental retardation exist and there is an overarching lack of knowledge about accessible treatment approaches for this population. Policy and practice recommendations are presented for disability and rehabilitation social workers in order to better understand and combat barriers to substance abuse treatment.

  6. Overcoming barriers to the mobilisation of patients in an intensive care unit.

    PubMed

    Dafoe, S; Chapman, M J; Edwards, S; Stiller, K

    2015-11-01

    We conducted a quality improvement project aimed at increasing the frequency of mobilisation in our ICU. We designed a four-part quality improvement project comprising: an audit documenting the baseline frequency of mobilisation; a staff survey evaluating perceptions of the barriers to mobilisation; identification of barriers that were amenable to change and implementation of strategies to address these; and a follow-up audit to determine their effectiveness. The setting was a tertiary care, urban, public hospital ICU in South Australia. All patients admitted to the ICU during the two audit periods were included in the audits, while all permanent/semi-permanent ICU staff were eligible for inclusion in the staff survey. We found that patient- and institution-related factors had the greatest impact on the mobilisation of patients in our ICU. Barriers identified as being amenable to change included insufficient staff education about the benefits of mobilisation, poor interdisciplinary communication and lack of leadership regarding mobilisation. Various strategies were implemented to address these barriers over a three-month period. Multivariable analyses showed that three out of four mobility outcomes did not significantly change between the baseline and follow-up audits, with a significant difference in favour of the baseline audit found for the fourth mobility outcome (maximum level of mobility). We concluded that implementing relatively simple measures to improve staff education, interdisciplinary communication and leadership regarding early progressive mobilisation was ineffective at improving mobility outcomes for patients in a large tertiary-level Australian ICU. Other strategies, such as changing sedation practices and/or increasing staffing, may be required to improve mobility outcomes of these patients.

  7. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

    PubMed Central

    Sun, Yujia; Nien, Chung-Yi; Chen, Kai; Liu, Hsiao-Yun; Johnston, Jeff; Zeitlinger, Julia; Rushlow, Christine

    2015-01-01

    The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner. PMID:26335633

  8. Oculocutaneous albinism: identifying and overcoming barriers to vision care in a Nigerian population.

    PubMed

    Udeh, N N; Eze, B I; Onwubiko, S N; Arinze, O C; Onwasigwe, E N; Umeh, R E

    2014-06-01

    To assess eye care service utilization, and identify access barriers in a south-eastern Nigerian albino population. The study was a population-based, cross-sectional survey conducted in Enugu state between August, 2011 and January, 2012. Using the data base of the state's Albino Foundation and tailored awareness creation, persons living with albinism were identified and recruited at two study centres. Data on participants' socio-demographics, perception of vision, visual needs, previous eye examination and or low vision assessment, use of glasses or low vision devices were collected. Reasons for non-utilisation of available vision care services were also obtained. Descriptive and comparative statistics were performed. A p < 0.05 was considered statistically significant. The participants (n = 153; males 70; females 83; sex ratio: 1:1.1) were aged 23.46 + 10.44 SD years (range 6-60 years). Most--95.4 % of the participants had no previous low vision assessment and none--0.0% had used low vision device. Of the participants, 82.4% reported previous eye examination, 33.3% had not used spectacles previously, despite the existing need. Ignorance--88.9% and poor access--8.5% were the main barriers to uptake of vision care services. In Enugu, Nigeria, there is poor awareness and low utilization of vision care services among people with albinism. The identified barriers to vision care access are amenable to awareness creation and logistic change in the provision of appropriate vision care services.

  9. Coping with structural disadvantage: Overcoming negative effects of perceived barriers through bonding identities.

    PubMed

    Bakouri, Mouna; Staerklé, Christian

    2015-12-01

    Members of socially disadvantaged groups often experience societal devaluation, material hardship, and restricted opportunities, especially during critical life-course transitions. In this study, we investigate whether what we term 'bonding identities', that is identities connecting the self to significant persons whether in terms of social relationships (e.g., family relations) or in terms of categorical collective identities, help individuals negotiate structural constraints on life-course opportunities. We develop and test a model according to which greater perceived barriers to one's life projects are psychologically harmful. We then test whether bonding identities function as a buffer against these stressors' negative psychological effects. Data were collected with a standardized questionnaire from pre-apprentices, apprentices, and young employees in two institutions (N = 365). Results confirm that perceiving barriers to one's life project was harmful for self-esteem. However, for participants who defined themselves in terms of bonding identities, greater perceived barriers did not decrease their perceived coping efficacy and were less harmful for their self-esteem. These findings point to the empowering role of bonding identities (and the social relationships that they imply) for disadvantaged group members.

  10. Overcoming barriers in care for the dying: Theoretical analysis of an innovative program model.

    PubMed

    Wallace, Cara L

    2016-08-01

    This article explores barriers to end-of-life (EOL) care (including development of a death denying culture, ongoing perceptions about EOL care, poor communication, delayed access, and benefit restrictions) through the theoretical lens of symbolic interactionism (SI), and applies general systems theory (GST) to a promising practice model appropriate for addressing these barriers. The Compassionate Care program is a practice model designed to bridge gaps in care for the dying and is one example of a program offering concurrent care, a recent focus of evaluation though the Affordable Care Act. Concurrent care involves offering curative care alongside palliative or hospice care. Additionally, the program offers comprehensive case management and online resources to enrollees in a national health plan (Spettell et al., 2009).SI and GST are compatible and interrelated theories that provide a relevant picture of barriers to end-of-life care and a practice model that might evoke change among multiple levels of systems. These theories promote insight into current challenges in EOL care, as well as point to areas of needed research and interventions to address them. The article concludes with implications for policy and practice, and discusses the important role of social work in impacting change within EOL care.

  11. Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence.

    PubMed

    Geoghegan, Jemma L; Senior, Alistair M; Holmes, Edward C

    2016-08-31

    Emerging diseases are a major challenge to public health. Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence. In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission. To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus. We considered the possibility of acquiring the necessary host adaptive mutations both before ('off-the-shelf' emergence) and after ('tailor-made' emergence) a virus is transmitted from a donor to a new recipient species. Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier. In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow. Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species.

  12. AccessAbility: Overcoming Information Barriers. Proceedings from the 1987 Spring Meeting of the Nebraska Library Association, College and University Section (Omaha, Nebraska, May 29, 1987).

    ERIC Educational Resources Information Center

    Kacena, Barbara J., Ed.

    Various aspects of the theme, "AccessAbility: Overcoming Information Barriers," are considered in the conference papers collected in this document. They include: (1) "The Library Image: A Barrier to Accessibility" (Janice S. Boyer); (2) "The Educationally Disadvantaged Student: How Can the Library Help?" (Michael Poma…

  13. OVERCOMING THE METER BARRIER AND THE FORMATION OF SYSTEMS WITH TIGHTLY PACKED INNER PLANETS (STIPs)

    SciTech Connect

    Boley, A. C.; Morris, M. A.; Ford, E. B.

    2014-09-10

    We present a solution to the long outstanding meter barrier problem in planet formation theory. As solids spiral inward due to aerodynamic drag, they will enter disk regions that are characterized by high temperatures, densities, and pressures. High partial pressures of rock vapor can suppress solid evaporation, and promote collisions between partially molten solids, allowing rapid growth. This process should be ubiquitous in planet-forming disks, which may be evidenced by the abundant class of Systems with Tightly packed Inner Planets discovered by the NASA Kepler Mission.

  14. Overcoming barriers to addressing education problems with research design: a panel discussion.

    PubMed

    Yarris, Lalena M; Gruppen, Larry D; Hamstra, Stanley J; Anders Ericsson, K; Cook, David A

    2012-12-01

    A plenary panel session at the 2012 Academic Emergency Medicine consensus conference "Education Research in Emergency Medicine: Opportunities, Challenges, and Strategies for Success" discussed barriers educators face in imagining, designing, and implementing studies to address educational challenges. This proceedings article presents a general approach to getting started in education research. Four examples of studies from the medical education literature that illustrate a distinct way to approach specific research questions are discussed. The study designs used are applicable to a variety of education research problems in emergency medicine (EM). Potential applications of studies are discussed, as well as effects and lessons learned.

  15. Overcoming political, social and economic barriers to promote solar photovoltaic technology in a developing country

    SciTech Connect

    Wijesooriya, P.; Hande, H.; Gunaratne, L.

    1994-12-31

    This paper narrates the experiences of a private sector commercial company and that of a private developers (non-profit organization) in their efforts to promote solar PV in a developing country. The country chosen is Sri Lanka, in which a considerable PV effort has already been witnessed. However, substantial political, economic and social barriers exist which have hindered PV promotion in that country. The authors point that similar constraints may impede promotional efforts in many developing countries and recommend that a global paradigm to promote the technology must assign an important role to the issue of obstacles.

  16. [Overcoming language barriers with telephone interpreters: first experiences at a German children's hospital].

    PubMed

    Langer, Thorsten; Wirth, Stefan

    2014-01-01

    Language barriers in the care for patients with limited German language proficiency contribute to impaired quality of care, more frequent medical errors and decreased patient satisfaction. However, professional interpreters are not systematically used in Germany. We conducted a pilot study in a German paediatric hospital to explore the demand for an interpreter by conducting a survey among parents and to test the use of telephone interpreters. Eight percent of the respondents said they were interested in interpreter support. All physicians and parents using a telephone interpreter were very satisfied with the quality and the organisation of the service.

  17. Rural veteran access to healthcare services: investigating the role of information and communication technologies in overcoming spatial barriers.

    PubMed

    Schooley, Benjamin L; Horan, Thomas A; Lee, Pamela W; West, Priscilla A

    2010-04-01

    This multimethod pilot study examined patient and practitioner perspectives on the influence of spatial barriers to healthcare access and the role of health information technology in overcoming these barriers. The study included a survey administered to patients attending a Department of Veterans Affairs (VA) health visit, and a focus group with VA care providers. Descriptive results and focus group findings are presented. Spatial distance is a significant factor for many rural veterans when seeking healthcare. For this sample of rural veterans, a range of telephone, computer, and Internet technologies may become more important for accessing care as Internet access becomes more ubiquitous and as younger veterans begin using the VA health system. The focus group highlighted the negative impact of distance, economic considerations, geographic barriers, and specific medical conditions on access to care. Lack of adequate technology infrastructure was seen as an obstacle to utilization. This study discusses the need to consider distance, travel modes, age, and information technology infrastructure and adoption when designing health information technology to care for rural patients.

  18. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways.

    PubMed

    Li, Man; Zhao, Mengnan; Fu, Yao; Li, You; Gong, Tao; Zhang, Zhirong; Sun, Xun

    2016-04-28

    Facing the threat of highly variable virus infection, versatile vaccination systems are urgently needed. Intranasal mRNA vaccination provides a flexible and convenient approach. However, the nasal epithelium remains a major biological barrier to deliver antigens to nasal associated lymphoid tissue (NALT). To address this issue, a potent polymer-based intranasal mRNA vaccination system for HIV-1 treatment was synthesized using cationic cyclodextrin-polyethylenimine 2k conjugate (CP 2k) complexed with anionic mRNA encoding HIV gp120. The delivery vehicle containing CP 2k and mRNA overcame the epithelial barrier by reversibly opening the tight junctions, enhanced the paracellular delivery of mRNA and consequently minimized absorption of toxins in the nasal cavity. Together with the excellent intracellular delivery and prolonged nasal residence time, strong system and mucosal anti-HIV immune responses as well as cytokine productions were achieved with a balanced Th1/Th2/Th17 type. Our study provided the first proof of evidence that cationic polymers can be used as safe and potent intranasal mRNA vaccine carriers to overcome the nasal epithelial barrier. The safe and versatile polymeric delivery system represents a promising vaccination platform for infectious diseases.

  19. Rural Veteran Access to Healthcare Services: Investigating the Role of Information and Communication Technologies in Overcoming Spatial Barriers

    PubMed Central

    Schooley, Benjamin L; Horan, Thomas A; Lee, Pamela W; West, Priscilla A

    2010-01-01

    This multimethod pilot study examined patient and practitioner perspectives on the influence of spatial barriers to healthcare access and the role of health information technology in overcoming these barriers. The study included a survey administered to patients attending a Department of Veterans Affairs (VA) health visit, and a focus group with VA care providers. Descriptive results and focus group findings are presented. Spatial distance is a significant factor for many rural veterans when seeking healthcare. For this sample of rural veterans, a range of telephone, computer, and Internet technologies may become more important for accessing care as Internet access becomes more ubiquitous and as younger veterans begin using the VA health system. The focus group highlighted the negative impact of distance, economic considerations, geographic barriers, and specific medical conditions on access to care. Lack of adequate technology infrastructure was seen as an obstacle to utilization. This study discusses the need to consider distance, travel modes, age, and information technology infrastructure and adoption when designing health information technology to care for rural patients. PMID:20697468

  20. Overcoming research barriers in Chagas disease-designing effective implementation science.

    PubMed

    Henao-Martínez, Andrés F; Colborn, Kathryn; Parra-Henao, Gabriel

    2017-01-01

    Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial. Basic science research has introduced new concepts and knowledge for the parasite and vector biology as well as better understanding of the pathophysiology of the disease. These research findings nevertheless require effective and timely translation into clinical practice. Likewise, the design of new research projects should account for the multiple system-based barriers. Implementation science facilitates the applicability of research findings and identifies barriers to its execution. Creation of implementation science measures to reach and sustain research programs with greater potential to impact Chagas disease are lacking. This point of view proposes opportunities for implementation science in Chagas disease and strategies for researching effective interventions for preventing and treating the disease.

  1. Microneedles and other physical methods for overcoming the stratum corneum barrier for cutaneous gene therapy.

    PubMed

    Coulman, Sion; Allender, Chris; Birchall, James

    2006-01-01

    The outermost layer of skin, the epidermis, has developed formidable physical and immunological barrier properties that prevent infiltration of deleterious chemicals and pathogens. Consequently, transdermal delivery of medicaments is currently restricted to a limited number of low molecular weight drugs. As a corollary, there has been significant recent interest in providing strategies that disrupt or circumvent the principal physical barrier, the stratum corneum, for the efficient cutaneous delivery of macromolecular and nucleic acid based therapeutics. These strategies include: electrical methods, intradermal injection, follicular delivery, particle acceleration, laser ablation, radiofrequency ablation, microscission, and microneedles. The application of microfabricated microneedle arrays to skin creates transient pathways to enable transcutaneous delivery of drugs and macromolecules. Microneedle use is simple, pain-free, and causes no bleeding, with further advantages of convenient manufacture, distribution, and disposal. To date, microneedles have been shown to deliver drug, peptide, antigen, and DNA efficiently through skin. Robust and efficient microneedle designs and compositions can be inserted into the skin without fracture. Further progress in microneedle array design, microneedle application apparatus, and integrated formulation will confirm this methodology as a realistic clinical strategy for delivering a range of medicaments, including DNA, to and through skin.

  2. Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy.

    PubMed Central

    Marshall, Merville C.

    2007-01-01

    A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African-American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID:17722663

  3. Overcoming barriers to health-care access: A qualitative study among African migrants in Guangzhou, China.

    PubMed

    Lin, Lavinia; Brown, Katherine B; Hall, Brian J; Yu, Fan; Yang, Jingqi; Wang, Jason; Schrock, Joshua M; Bodomo, Adams B; Yang, Ligang; Yang, Bin; Nehl, Eric J; Tucker, Joseph D; Wong, Frank Y

    2016-10-01

    Guangzhou is China's third most populous city, and the region's burgeoning manufacturing economy has attracted many young African businessmen and entrepreneurs to the city. The aims of this study were to examine strategies that African migrants in Guangzhou have adopted in response to health-care barriers, and explore their perceptions of how to address their needs. Twenty-five semi-structured interviews and two focus groups were conducted among African migrants residing in Guangzhou, China. Facing multiple barriers to care, African migrants have adopted a number of suboptimal and unsustainable approaches to access health care. These included: using their Chinese friends or partners as interpreters, self-medicating, using personal connections to medical doctors, and travelling to home countries or countries that offer English-speaking doctors for health care. Health-care providers and health organisations in Guangzhou have not yet acquired sufficient cultural competence to address the needs of African migrants residing in the city. Introducing linguistically and culturally competent health-care services in communities concentrated with African migrants may better serve the population. With the growing international migration to China, it is essential to develop sustainable approaches to improving health-care access for international migrants, particularly those who are marginalised.

  4. Overcoming Workplace Barriers: A Focus Group Study Exploring African American Mothers' Needs for Workplace Breastfeeding Support

    PubMed Central

    Johnson, Angela Marie; Kirk, Rosalind; Muzik, Maria

    2015-01-01

    Background Persistent racial disparities in breastfeeding show that African American women breastfeed at the lowest rates. Return to work is a critical breastfeeding barrier for African American women who return to work sooner than other ethnic groups and more often encounter unsupportive work environments. They also face psychosocial burdens that make breastfeeding at work uniquely challenging. Participants share personal struggles with combining paid employment and breastfeeding and suggest workplace and personal support strategies that they believe will help continue breastfeeding after a return to work. Objective To explore current perspectives on ways to support African American mothers' workplace breastfeeding behavior. Methods Pregnant African American women (n = 8), African American mothers of infants (n = 21), and lactation support providers (n = 9) participated in 1 of 6 focus groups in the Greater Detroit area. Each focus group audiotape was transcribed verbatim. Thematic analysis was used to inductively analyze focus group transcripts and field notes. Focus groups explored thoughts, perceptions, and behavior on interventions to support African American women's breastfeeding. Results Participants indicate that they generally believed breastfeeding was a healthy option for the baby; however, paid employment is a critical barrier to successful breastfeeding for which mothers receive little help. Participants felt breastfeeding interventions that support working African American mothers should include education and training for health care professionals, regulation and enforcement of workplace breastfeeding support policies, and support from peers who act as breastfeeding role models. Conclusion Culturally appropriate interventions are needed to support breastfeeding among working African American women. PMID:25714345

  5. Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment

    PubMed Central

    Lorenz, Timo; Frischling, Cora; Cuadros, Raphael; Heinitz, Kathrin

    2016-01-01

    The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism–17 of them with autism-specific employment–participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems–problems with organizational and practical process-related aspects of the job entry–most frequently while individuals in non-autism-specific employment mentioned social problems–obstacles concerning communication and human interaction–most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths. PMID:26766183

  6. Overcoming restriction as a barrier to DNA transformation in Caldicellulosiruptor species results in efficient marker replacement

    PubMed Central

    2013-01-01

    Background Thermophilic microorganisms have special advantages for the conversion of plant biomass to fuels and chemicals. Members of the genus Caldicellulosiruptor are the most thermophilic cellulolytic bacteria known. They have the ability to grow on a variety of non-pretreated biomass substrates at or near ~80°C and hold promise for converting biomass to bioproducts in a single step. As for all such relatively uncharacterized organisms with desirable traits, the ability to genetically manipulate them is a prerequisite for making them useful. Metabolic engineering of pathways for product synthesis is relatively simple compared to engineering the ability to utilize non-pretreated biomass. Results Here we report the construction of a deletion of cbeI (Cbes2438), which encodes a restriction endonuclease that is as a major barrier to DNA transformation of C. bescii. This is the first example of a targeted chromosomal deletion generated by homologous recombination in this genus and the resulting mutant, JWCB018 (ΔpyrFA ΔcbeI), is readily transformed by DNA isolated from E. coli without in vitro methylation. PCR amplification and sequencing suggested that this deletion left the adjacent methyltransferase (Cbes2437) intact. This was confirmed by the fact that DNA isolated from JWCB018 was protected from digestion by CbeI and HaeIII. Plasmid DNA isolated from C. hydrothermalis transformants were readily transformed into C. bescii. Digestion analysis of chromosomal DNA isolated from seven Caldicellulosiruptor species by using nine different restriction endonucleases was also performed to identify the functional restriction-modification activities in this genus. Conclusion Deletion of the cbeI gene removes a substantial barrier to routine DNA transformation and chromosomal modification of C. bescii. This will facilitate the functional analyses of genes as well as metabolic engineering for the production of biofuels and bioproducts from biomass. An analysis of

  7. Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

    PubMed Central

    2010-01-01

    Background Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD). Methods The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches. Results Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face

  8. Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process.

    PubMed

    Latka, Agnieszka; Maciejewska, Barbara; Majkowska-Skrobek, Grazyna; Briers, Yves; Drulis-Kawa, Zuzanna

    2017-04-01

    Bacteriophages are bacterial viruses that infect the host after successful receptor recognition and adsorption to the cell surface. The irreversible adherence followed by genome material ejection into host cell cytoplasm must be preceded by the passage of diverse carbohydrate barriers such as capsule polysaccharides (CPSs), O-polysaccharide chains of lipopolysaccharide (LPS) molecules, extracellular polysaccharides (EPSs) forming biofilm matrix, and peptidoglycan (PG) layers. For that purpose, bacteriophages are equipped with various virion-associated carbohydrate active enzymes, termed polysaccharide depolymerases and lysins, that recognize, bind, and degrade the polysaccharide compounds. We discuss the existing diversity in structural locations, variable architectures, enzymatic specificities, and evolutionary aspects of polysaccharide depolymerases and virion-associated lysins (VALs) and illustrate how these aspects can correlate with the host spectrum. In addition, we present methods that can be used for activity determination and the application potential of these enzymes as antibacterials, antivirulence agents, and diagnostic tools.

  9. Evaluating Restorative Justice Circles of Support and Accountability: Can Social Support Overcome Structural Barriers?

    PubMed

    Bohmert, Miriam Northcutt; Duwe, Grant; Hipple, Natalie Kroovand

    2016-06-05

    In a climate in which stigmatic shaming is increasing for sex offenders as they leave prison, restorative justice practices have emerged as a promising approach to sex offender reentry success and have been shown to reduce recidivism. Criminologists and restorative justice advocates believe that providing ex-offenders with social support that they may not otherwise have is crucial to reducing recidivism. This case study describes the expressive and instrumental social support required and received, and its relationship to key outcomes, by sex offenders who participated in Circles of Support and Accountability (COSAs), a restorative justice, reentry program in Minnesota. In-depth interviews with re-entering sex offenders and program volunteers revealed that 75% of offenders reported weak to moderate levels of social support leaving prison, 70% reported receiving instrumental support in COSAs, and 100% reported receiving expressive support. Findings inform work on social support, structural barriers, and restorative justice programming during sex offender reentry. © The Author(s) 2016.

  10. Learning from the best: Overcoming barriers to reforms-based elementary science teaching

    NASA Astrophysics Data System (ADS)

    Banchi, Heather May

    This study explored the characteristics of elementary science teachers who employ reforms-based practices. Particular attention was paid to the consistency of teachers' practices and their beliefs, the impact of professional development experiences on practices, and how teachers mitigated barriers to reforms-based instruction. Understanding how successful elementary science teachers develop fills a gap in the science reforms literature. Participants included 7 upper elementary science teachers from six different schools. All schools were located within two suburban school districts in the south-Atlantic United States and data was collected during the spring of 2008. Data collection included use of the Reformed Teaching Observation Protocol (RTOP) to evaluate the level of reforms-based instruction, as well as 35 hours of classroom observation field notes and 21 hours of audio-taped teacher interviews. The variety of data sources allowed for triangulation of evidence. The RTOP was analyzed using descriptive statistics and classroom observations and interview data were analyzed using Erickson's (1986) guidelines for analytic induction. Findings indicated (a) reforms-based elementary science teaching was attainable, (b) beliefs and practices were consistent and both reflected reforms-based philosophies and practices, (c) formal professional development experiences were limited and did not foster reforms-based practices, (d) informal professional development pursued by teachers had a positive impact on practices, (e) barriers to reforms-based instruction were present but mitigated by strong beliefs and practical strategies like curriculum integration. These findings suggest that there are common, salient characteristics of reforms-based teachers' beliefs, practices, and professional development experiences. These commonalities contribute to an understanding of how reforms-based teachers develop, and inform efforts to move all elementary teachers in the direction of

  11. Cycles of silence: First Nations women overcoming social and historical barriers in supportive cancer care.

    PubMed

    Hammond, Chad; Thomas, Roanne; Gifford, Wendy; Poudrier, Jennifer; Hamilton, Ryan; Brooks, Carolyn; Morrison, Tricia; Scott, Tracy; Warner, Doris

    2017-02-01

    First Nations people with cancer in Canada confront several critical inequities in physical and psychosocial domains. First Nations women are at a particular disadvantage as they are disproportionately affected by social determinants of health, but how they navigate these challenges within their communities is poorly understood. Our study explores survivorship experiences of First Nations women with cancer and their caregivers. Drawing from a larger data set on survivorship, we identify several major barriers to cancer communication and support in First Nations communities. Our team conducted a participatory, arts-based study using several data collection methods (interviews, sharing sessions, photovoice, and other creative activities) with 43 participants (24 cancer survivors and 19 caregivers) from four First Nations communities in Canada. Two major themes have emerged out of our data analyses: (1) suffering without support leads to cycles of silence and (2) community-based supports can disrupt these cycles. We identified several social, historical, and institutional barriers to speaking about cancer and finding/providing support; however, communities met the challenge of silence through voluntary and unsolicited provision of support. Widespread silence around cancer reflects both the limited access First Nations people have to formal, supportive programs and services, as well as the creative ways they provide emotional, social, and financial support within their informal networks. Beyond the support of their communities, they also required institutional provision of care that is culturally safe, addressing the colonial impacts on cancer communication and the disproportionate burdens of disease in First Nations communities. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers

    PubMed Central

    Bruce, Alex; Faunce, Thomas

    2015-01-01

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen–consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power. PMID:26052427

  13. Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos.

    PubMed

    Masaki, Hideki; Kato-Itoh, Megumi; Takahashi, Yusuke; Umino, Ayumi; Sato, Hideyuki; Ito, Keiichi; Yanagida, Ayaka; Nishimura, Toshinobu; Yamaguchi, Tomoyuki; Hirabayashi, Masumi; Era, Takumi; Loh, Kyle M; Wu, Sean M; Weissman, Irving L; Nakauchi, Hiromitsu

    2016-11-03

    Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17(+) endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17(+) endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Sustainable fuel, food, fertilizer and ecosystems through a global artificial photosynthetic system: overcoming anticompetitive barriers.

    PubMed

    Bruce, Alex; Faunce, Thomas

    2015-06-06

    This article discusses challenges that artificial photosynthetic (AP) systems will face when entering and competing in a global market characterized by established fossil fuel technology. It provides a perspective on the neoliberal principles underpinning much policy entrenching such environmentally destructive technology and outlines how competition law could aid overcoming these hurdles for AP development. In particular, it critiques the potential for competition law to promote a global AP initiative with greater emphasis on atmospheric carbon dioxide and nitrogen fixation (as well as solar-driven water splitting) to produce an equitable, globally distributed source of human food, fertilizer and biosphere sustainability, as well as hydrogen-based fuel. Some relevant strategies of competition law evaluated in this context include greater citizen-consumer involvement in shaping market values, legal requirements to factor services from the natural environment (i.e. provision of clean air, water, soil pollution degradation) into corporate costs, reform of corporate taxation and requirements to balance maximization of shareholder profit with contribution to a nominated public good, a global financial transactions tax, as well as prohibiting horizontal cartels, vertical agreements and unilateral misuse of market power.

  15. Overcoming barriers to a research-ready national commercial claims database.

    PubMed

    Newman, David; Herrera, Carolina-Nicole; Parente, Stephen T

    2014-11-01

    Billions of dollars have been spent on the goal of making healthcare data available to clinicians and researchers in the hopes of improving healthcare and lowering costs. However, the problems of data governance, distribution, and accessibility remain challenges for the healthcare system to overcome. In this study, we discuss some of the issues around holding, reporting, and distributing data, including the newest "big data" challenge: making the data accessible to researchers and policy makers. This article presents a case study in "big healthcare data" involving the Health Care Cost Institute (HCCI). HCCI is a nonprofit, nonpartisan, independent research institute that serves as a voluntary repository of national commercial healthcare claims data. Governance of large healthcare databases is complicated by the data-holding model and further complicated by issues related to distribution to research teams. For multi-payer healthcare claims databases, the 2 most common models of data holding (mandatory and voluntary) have different data security requirements. Furthermore, data transport and accessibility may require technological investment. HCCI's efforts offer insights from which other data managers and healthcare leaders may benefit when contemplating a data collaborative.

  16. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    NASA Astrophysics Data System (ADS)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  17. Obtaining family consent for participation in Alzheimer's research in a Cuban-American population: strategies to overcome the barriers.

    PubMed

    Williams, C L; Tappen, R; Buscemi, C; Rivera, R; Lezcano, J

    2001-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder's comfort (tranquilidad) and solitude (soledad). Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms.

  18. OVERCOMING BARRIERS To DIVERSITY IN CHIROPRACTIC PATIENT AND PRACTITIONER POPULATIONS: A COMMENTARY.

    PubMed

    Young, Kenneth J

    2015-01-01

    Increasing the diversity of practitioner and patient populations has been identified as a worthy goal in the chiropractic profession, which has predominantly white male practitioners and white female patients in the USA. Toward that end, 'diversity' has been the topic of several papers and was the theme of a 2012 conference of chiropractic educators. However, generally just the microcosm of the interactions of practitioners with patients or teachers with students has been discussed. The macrocosm of larger societal issues and government policies has not been broached. Examples of issues and policies that affect diversity within a profession include portrayals of, and value judgements on diversity by the media and politicians, as well as public funding for healthcare and education. Diversity was defined in this paper to mean differences in race, sex, sexual orientation, economic status, ethnicity, religion and other life circumstances in a population. The purpose of this paper is to raise awareness of evidence that social issues and government policy affect the diversity of practitioners and patients, and to suggest that the barriers to diversity present in these realms be addressed with a cogent, profession-wide effort in order to help increase the diversity of people involved with chiropractic.

  19. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    PubMed

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  20. [Google translate is not sufficient to overcome language barriers in neonatal medicine].

    PubMed

    Börner, N; Sponholz, S; König, K; Brodkorb, S; Bührer, C; Roehr, C C

    2013-12-01

    Language barriers hinder the interaction with patients and relatives. The use of language services increases knowledge, satisfaction and the use of medical care and thus improves patient's clinical outcome. The recommended use of professional interpreters (PI) is not always feasible. We tested an online translation tool as an alternative for PI for the transla-tion of standardized sentences from a neonatal doctor-/nurse-relative-interview.Translation of 20 sentences from a German neonatal intensive care unit parent information brochure to English, Portuguese and Arabic, using Google Translate (GT). Assessment of accuracy concerning grammar and content, in a second step simplification of all incorrect sentences, translation by GT and critical re-assessment and evaluation.An average of 42% of the sentences was correctly translated concerning grammar and content. The proportion of incorrectly translated sentences varied between 45-70%. By simpli-fication another 23% were translated correctly.Translations by GT were often incorrect in content and grammar. We suppose that the design of GT, which is a statistical translation engine, might be an explanation for this phenomenon. Presently, GT cannot guarantee unambiguous translations and cannot substitute PIs, only in particular circumstances, the use of GT or similar engines may be justified. For future use of electronic translation services, we suggest to compile a catalogue of sentences containing central information, which can be translated into defined foreign languages without misinterpretation or loss of information. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Pregnancy options counseling for adolescents: overcoming barriers to care and preserving preference.

    PubMed

    Dobkin, Loren M; Perrucci, Alissa C; Dehlendorf, Christine

    2013-04-01

    Current clinical guidelines for counseling adolescent patients about their pregnancy options fail to give concrete suggestions for how to begin and hold conversations that support patient autonomy, provide accurate and unbiased information, and address barriers to care. Recent research suggests that relative to adult women, adolescents are at increased risk of being denied abortion because they present beyond facilities' gestational age limits. Counseling that neglects to address the structural and developmental challenges that adolescents face when seeking care may contribute to the risk of abortion denial as well as subsequent delays in prenatal care. The task of providing non-directive, patient-centered, evidence-based pregnancy options counseling to an adolescent while ensuring that she receives her chosen course of care in a timely manner is challenging. This article presents a shared decision-making framework and specific suggestions for healthcare providers to support adolescent patients in coming to their decision about whether to continue or terminate an unplanned pregnancy and access follow-up care within the current sociopolitical environment.

  2. Overcoming barriers and thresholds – signaling of oligomeric Aβ through the prion protein to Fyn

    PubMed Central

    2013-01-01

    Evidence has been mounting for an involvement of the prion protein (PrP) in a molecular pathway assumed to play a critical role in the etiology of Alzheimer disease. A currently popular model sees oligomeric amyloid β (oAβ) peptides bind directly to PrP to emanate a signal that causes activation of the cytoplasmic tyrosine kinase Fyn, an essential player in a cascade of events that ultimately leads to NMDA receptor-mediated excitotoxicity and hyper-phosphorylation of tau. The model does not reveal, however, how extracellular binding of oAβ to PrP is communicated across the plasma membrane barrier to affect activation of Fyn. A scenario whereby PrP may adapt a transmembrane topology to affect Fyn activation in the absence of additional partners is currently not supported by evidence. A survey of known candidate PrP interactors leads to a small number of molecules that are known to acquire a transmembrane topology and understood to contribute to Fyn activation. Because multiple signaling pathways converge onto Fyn, a realistic model needs to take into account a reality of Fyn acting as a hub that integrates signals from multiple inhibitory and activating effectors. To clarify the role of PrP in oAβ-dependent excitotoxicity, future studies may need to incorporate experimental designs that can probe the contributions of Fyn modulator pathways and rely on analogous readouts, rather than threshold effects, known to underlie excitotoxic signaling. PMID:23856335

  3. Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting

    PubMed Central

    Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

    2017-01-01

    The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful. PMID:28184152

  4. Ex vivo expanded hematopoietic stem cells overcome the MHC barrier in allogeneic transplantation

    PubMed Central

    Zheng, Junke; Umikawa, Masato; Zhang, Shichuan; Huynh, HoangDinh; Silvany, Robert; Chen, Benjamin P.C.; Chen, Lieping; Zhang, Cheng Cheng

    2011-01-01

    Summary The lack of understanding of the interplay between hematopoietic stem cells (HSCs) and the immune system has severely hampered the stem cell research and practice of transplantation. Major problems for allogeneic transplantation include low levels of donor engraftment and high risks of graft-versus-host disease (GVHD). Transplantation of purified allogeneic HSCs diminishes the risk of GVHD, but results in decreased engraftment. Here we show that ex vivo expanded mouse HSCs efficiently overcame the major histocompatibility complex barrier and repopulated allogeneic recipient mice. An 8-day expansion culture led to a 40-fold increase of the allograft ability of HSCs. Both increased numbers of HSCs and culture-induced elevation of expression of the immune inhibitor CD274 (B7-H1 or PD-L1) on the surface of HSCs contributed to the enhancement. Our study indicates the great potential of utilizing ex vivo expanded HSCs for allogeneic transplantation, and suggests that the immune privilege of HSCs can be modulated. PMID:21816363

  5. Drug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting.

    PubMed

    Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

    2017-01-01

    The blood-brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful.

  6. Overcoming Spatial and Temporal Barriers to Public Access Defibrillators Via Optimization.

    PubMed

    Sun, Christopher L F; Demirtas, Derya; Brooks, Steven C; Morrison, Laurie J; Chan, Timothy C Y

    2016-08-23

    Immediate access to an automated external defibrillator (AED) increases the chance of survival for out-of-hospital cardiac arrest (OHCA). Current deployment usually considers spatial AED access, assuming AEDs are available 24 h a day. The goal of this study was to develop an optimization model for AED deployment, accounting for spatial and temporal accessibility, to evaluate if OHCA coverage would improve compared with deployment based on spatial accessibility alone. This study was a retrospective population-based cohort trial using data from the Toronto Regional RescuNET Epistry cardiac arrest database. We identified all nontraumatic public location OHCAs in Toronto, Ontario, Canada (January 2006 through August 2014) and obtained a list of registered AEDs (March 2015) from Toronto Paramedic Services. Coverage loss due to limited temporal access was quantified by comparing the number of OHCAs that occurred within 100 meters of a registered AED (assumed coverage 24 h per day, 7 days per week) with the number that occurred both within 100 meters of a registered AED and when the AED was available (actual coverage). A spatiotemporal optimization model was then developed that determined AED locations to maximize OHCA actual coverage and overcome the reported coverage loss. The coverage gain between the spatiotemporal model and a spatial-only model was computed by using 10-fold cross-validation. A total of 2,440 nontraumatic public OHCAs and 737 registered AED locations were identified. A total of 451 OHCAs were covered by registered AEDs under assumed coverage 24 h per day, 7 days per week, and 354 OHCAs under actual coverage, representing a coverage loss of 21.5% (p < 0.001). Using the spatiotemporal model to optimize AED deployment, a 25.3% relative increase in actual coverage was achieved compared with the spatial-only approach (p < 0.001). One in 5 OHCAs occurred near an inaccessible AED at the time of the OHCA. Potential AED use was significantly improved

  7. Bryozoan diversity around the Falkland and South Georgia Islands: Overcoming Antarctic barriers.

    PubMed

    Figuerola, Blanca; Barnes, David K A; Brickle, Paul; Brewin, Paul E

    2017-05-01

    There are a number of remote archipelagos distributed between 45 and 60 °S. The biota of these islands provide useful information to describe and understand patterns in biodiversity and biogeography as well as potential impacts of climate change on marine ecosystems. They are in key locations either side of the Polar Front but also have limited influence from human activities. Here we investigate one taxon, bryozoans, on South Atlantic shelf habitats of the Falkland (FI) and the sub-Antarctic island of South Georgia (SG). We present new data on spatial distribution in these islands, as well as an analysis of the bryozoological similarities between these and neighbouring regions. A total of 85 species of cheilostome bryozoans (351 samples) were found, belonging to 33 genera, including 18 potentially new genera and 23 new species. Remarkably 65% and 41% of species were reported for the first time at FI and SG, respectively. The highest and the lowest value of species richness and species/genus ratio were found at East (EFI) and West Falkland (WFI), respectively, likely showing a tendency for stronger intrageneric competition. New data from this study were jointly analysed with data from the literature and existing databases, revealing new bathymetric ranges in 32 species. The biogeographic affinities of the bryozoans found give further evidence of the hypothesis of sequential separation of Gondwana and support the changing concept that although the Polar Front acts as a circumpolar biogeographic barrier it is not as impermeable as originally thought. Potential dispersal mechanisms are also discussed.

  8. Identifying and Overcoming Critical Barriers to Widespread Second Use of PEV Batteries

    SciTech Connect

    Neubauer, J.; Smith, K.; Wood, E.; Pesaran, A.

    2015-02-01

    Both the market penetration of plug-in electric vehicles (PEVs) and deployment of grid-connected energy storage systems are presently restricted by the high cost of batteries. Battery second use (B2U) strategies--in which a single battery first serves an automotive application, then is redeployed into a secondary market--could help address both issues by reducing battery costs to the primary (automotive) and secondary (electricity grid) users. This study investigates the feasibility of and major barriers to the second use of lithium-ion PEV batteries by posing and answering the following critical B2U questions: 1. When will used automotive batteries become available, and how healthy will they be? 2. What is required to repurpose used automotive batteries, and how much will it cost? 3. How will repurposed automotive batteries be used, how long will they last, and what is their value? Advanced analysis techniques are employed that consider the electrical, thermal, and degradation response of batteries in both the primary (automotive) and secondary service periods. Second use applications are treated in detail, addressing operational requirements, economic value, and market potential. The study concludes that B2U is viable and could provide considerable societal benefits due to the large possible supply of repurposed automotive batteries and substantial remaining battery life following automotive service. However, the only identified secondary market large enough to consume the supply of these batteries (utility peaker plant replacement) is expected to be a low margin market, and thus B2U is not expected to affect the upfront cost of PEVs.

  9. Primary care resident, faculty, and patient views of barriers to cultural competence, and the skills needed to overcome them.

    PubMed

    Shapiro, Johanna; Hollingshead, Judy; Morrison, Elizabeth H

    2002-08-01

    Primary care residencies are expected to provide training in cultural competence. However, we have insufficient information about the perceptions of stakeholders actually involved in healthcare (i.e. residents, faculty and patients) regarding commonly encountered cross-cultural barriers and the skills required to overcome them. This study used a total of 10 focus groups to explore resident, faculty and patient attitudes and beliefs about what culturally competent doctor-patient communication means, what obstacles impede or prevent culturally competent communication, and what kinds of skills are helpful in achieving cultural competence. A content analysis was performed to identify major themes. Residents and faculty defined culturally competent communication in terms of both generic and culture-specific elements, however, patients tended to emphasize only generic attitudes and skills. Residents and patients were liable to blame each other in explaining barriers; faculty were more likely to consider systemic influences contributing to resident-patient difficulties. All groups emphasized appropriate skill and attitude development in learners as the key to successful communication. However, residents were sceptical of sensitivity and communication skills training, and worried that didactic presentations would result in cultural stereotyping. All stakeholders recognized the importance of effective doctor-patient communication. Of concern was the tendency of various stakeholders to engage in person-blame models.

  10. Applying Risk Science and Stakeholder Engagement to Overcome Environmental Barriers to Marine and Hydrokinetic Energy Projects

    SciTech Connect

    Copping, Andrea E.; Anderson, Richard M.; Van Cleve, Frances B.

    2010-09-20

    The production of electricity from the moving waters of the ocean has the potential to be a viable addition to the portfolio of renewable energy sources worldwide. The marine and hydrokinetic (MHK) industry faces many hurdles, including technology development, challenges of offshore deployments, and financing; however, the barrier most commonly identified by industry, regulators, and stakeholders is the uncertainty surrounding potential environmental effects of devices placed in the water and the permitting processes associated with real or potential impacts. Regulatory processes are not well positioned to judge the severity of harm due to turbines or wave generators. Risks from MHK devices to endangered or protected animals in coastal waters and rivers, as well as the habitats that support them, are poorly understood. This uncertainty raises concerns about catastrophic interactions between spinning turbine blades or slack mooring lines and marine mammals, birds and fish. In order to accelerate the deployment of tidal and wave devices, there is a need to sort through the extensive list of potential interactions that may cause harm to marine organisms and ecosystems, to set priorities for regulatory triggers, and to direct future research. Identifying the risk of MHK technology components on specific marine organisms and ecosystem components can separate perceived from real risk-relevant interactions. Scientists from Pacific Northwest National Laboratory (PNNL) are developing an Environmental Risk Evaluation System (ERES) to assess environmental effects associated with MHK technologies and projects through a systematic analytical process, with specific input from key stakeholder groups. The array of stakeholders interested in the development of MHK is broad, segmenting into those whose involvement is essential for the success of the MHK project, those that are influential, and those that are interested. PNNL and their partners have engaged these groups, gaining

  11. Overcoming educational barriers for advance care planning in Latinos with video images.

    PubMed

    Volandes, Angelo E; Ariza, Miguel; Abbo, Elmer D; Paasche-Orlow, Michael

    2008-06-01

    culture that may actually reflect inadequate comprehension. Attention to communication barriers with techniques like the video used in the current study may help ensure optimal end-of-life care for Latino patients irrespective of educational level.

  12. Performance of some new Niño3.4 predictors at overcoming the spring predictability barrier.

    NASA Astrophysics Data System (ADS)

    Miguel, Tasambay-Salazar; Jose, Ortizbevia Maria; Francisco Jose, Alvarez-Garcia; Antonio, Ruizdeelvira

    2016-04-01

    The El Niño-Southern Oscillation (ENSO) phenomenon is the main source of predictability skill in many regions of the world, at seasonal and interannual timescales. Improving ENSO understanding and forecast skill is still one of the main goals of the international seasonal forecast programs. A common feature found in ENSO forecast is the skill predictability barrier, that is the skill drop for forecast across the spring season. In this study ENSO variability is represented by the Niño3.4 Index. Here we will use different seasonal linear stochastic models to test the performance of some new ENSO predictors at overcoming the spring predictability barrier. The benchmarkt is the performance scored by the same predictive scheme when the variables are those of a basic equatorial model representing the 'recharge-discharge' oscillator paradigm. Some of the new predictors, like the Tropical South Atlantic Index, the Tropical North Atlantic Index, the Indian Ocean Dipole Mode or the Pacific Meridional Model have been pointed at by recent studies. Additionally, we propose two new predictors, that take into account the zonal sea surface temperature gradients across the tropical Pacific, the North Tropical Pacific Zonal Gradient and the South Tropical Pacific Zonal Gradient Indexes. We intercompare the performance of the new predictors, by introducing them, one at a time, in a simple, three variables, stochastic predictive scheme. For some seasons and lags, the differences between the skill scored by some of the models that include one of these predictors are important. However, these are diminished when a Full Stochastic Mode set-up is adopted. References. Tasambay Salazar, M.; Ortiz Beviá, M. J.; Alvarez García, F. J.; Ruiz de Elvira Serra, A. The Niño3.4 region predictability beyond the persistence barrier. Tellus A. 2015, 67. doi: 10.3402/tellusa.v67.27457,

  13. Barriers to integration of behavioral and social sciences in the general medicine curriculum and recommended strategies to overcome them: A systematic review

    PubMed Central

    TABATABAEI, ZAHRA; YAZDANI, SHAHRAM; SADEGHI, RAMIN

    2016-01-01

    Introduction The integration of behavioral and social sciences (BSS) into the curriculum of medical students in order to equip them with the necessary knowledge, skills and attitudes is an essential issue, emphasized in many researches. Our aim is to investigate the barriers to integrate BSS into the general medicine curriculum as well as the recommended strategies to overcome such barriers through a systematic review of literature. Methods PubMed, ERIC, Scopus, CINAHL, Google Scholar, and OPENGREY were searched for studies on the barriers to integration of BSS into the general medicine curriculum as well as the strategies employed to overcome them until August 28, 2015. Results Sixteen relevant studies were included and the related domains were categorized as barriers and some strategies were recommended to overcome them. In addition, the quality of the included studies was assessed. Conclusion Despite the prominent role of BSS in the effectiveness of health care, these sciences have not been included in the curriculum of medical students effectively. The identified barriers and the strategies used to overcome them should be considered for all integration programs. Future studies should focus on the process of BSS integration in the medical curricula and should evaluate the efficacy of this integration in more detail. PMID:27382578

  14. Let’s Not Contribute to Disparities: The Best Methods for Teaching Clinicians How to Overcome Language Barriers to Health Care

    PubMed Central

    Jacobs, Elizabeth A.

    2010-01-01

    Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching “Medical Spanish” or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one’s own limited non-English language skills. PMID:20352518

  15. The GEOFAR Project - Geothermal Finance and Awareness in Europeans Regions - Development of new schemes to overcome non-technical barriers, focusing particularly on financial barriers

    NASA Astrophysics Data System (ADS)

    Poux, Adeline; Wendel, Marco; Jaudin, Florence; Hiegl, Mathias

    2010-05-01

    Numerous advantages of geothermal energy like its widespread distribution, a base-load power and availability higher than 90%, a small footprint and low carbon emissions, and the growing concerns about climate changes strongly promote the development of geothermal projects. Geothermal energy as a local energy source implies needs on surface to be located close to the geothermal resource. Many European regions dispose of a good geothermal potential but it is mostly not sufficiently developed due to non-technical barriers occurring at the very early stages of the project. The GEOFAR Project carried out within the framework of EU's "Intelligent Energy Europe" (IEE) program, gathers a consortium of European partners from Germany, France, Greece, Spain and Portugal. Launched in September 2008, the aim of this research project is to analyze the mentioned non-technical barriers, focusing most particularly on economic and financial aspects. Based on this analysis GEOFAR aims at developing new financial and administrative schemes to overcome the main financial barriers for deep geothermal projects (for electricity and direct use, without heat pumps). The analysis of the current situation and the future development of geothermal energy in GEOFAR target countries (Germany, France, Greece, Spain, Portugal, Slovakia, Bulgaria and Hungary) was necessary to understand and expose the diverging status of the geothermal sector and the more and less complicated situation for geothermal projects in different Europeans Regions. A deeper analysis of 40 cases studies (operating, planned and failed projects) of deep geothermal projects also contributed to this detailed view. An exhaustive analysis and description of financial mechanisms already existing in different European countries and at European level to support investors completed the research on non-technical barriers. Based on this profound analysis, the GEOFAR project has made an overview of the difficulties met by project

  16. Cell-to-cell transmission can overcome multiple donor and target cell barriers imposed on cell-free HIV.

    PubMed

    Zhong, Peng; Agosto, Luis M; Ilinskaya, Anna; Dorjbal, Batsukh; Truong, Rosaline; Derse, David; Uchil, Pradeep D; Heidecker, Gisela; Mothes, Walther

    2013-01-01

    Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication cycle are efficiently supported in highly permissive cells. However, when the cell-free path was systematically hindered at various steps, HIV transmission became contact-dependent. Cell-to-cell transmission overcame barriers introduced in the donor cell at the level of gene expression and surface retention by the restriction factor tetherin. Moreover, neutralizing antibodies that efficiently inhibit cell-free HIV were less effective against cell-to-cell transmitted virus. HIV cell-to-cell transmission also efficiently infected target T cells that were relatively poorly susceptible to cell-free HIV. Importantly, we demonstrate that the donor and target cell types influence critically the extent by which cell-to-cell transmission can overcome each barrier. Mechanistically, cell-to-cell transmission promoted HIV spread to more cells and infected target cells with a higher proviral content than observed for cell-free virus. Our data demonstrate that the frequently observed contact-dependent spread of HIV is the result of specific features in donor and target cell types, thus offering an explanation for conflicting reports on the extent of cell-to-cell transmission of HIV.

  17. CAI: Overcoming Attitude Barriers.

    ERIC Educational Resources Information Center

    Netusil, Anton J.; Kockler, Lois H.

    During each of two school quarters, approximately 60 college students enrolled in a mathematics course were randomly assigned to an experimental group or a control group. The control group received instruction by the lecture method only; the experimental group received the same instruction, except that six computer-assisted instruction (CAI) units…

  18. miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

    PubMed Central

    Mandrekar-Colucci, Shweta; Hall, Jodie C.E.; Sweet, David R.; Schmitt, Philipp J.; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia

    2016-01-01

    Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails

  19. The role of "blebbing" in overcoming the hydrophobic barrier during biooxidation of elemental sulfur by Thiobacillus thiooxidans

    USGS Publications Warehouse

    Knickerbocker, C.; Nordstrom, D.K.; Southam, G.

    2000-01-01

    Brimstone Basin, in southeastern Yellowstone National Park, Wyoming is an ancient hydrothermal area containing solfataric alteration. Drainage waters flowing from Brimstone Basin had pH values as low as 1.23 and contained up to 1.7×106 MPN/ml acidophilic sulfur-oxidizing bacteria. Thiobacillus thiooxidans was the dominant sulfur-oxidizing bacterium recovered from an enrichment culture and was used in a structural examination of bacterial sulfur oxidation. Growth in these sulfur cultures occurred in two phases with cells in association with the macroscopic sulfur grains and in suspension above these grains. Colonization of sulfur grains by individual cells and microcolonies was facilitated by organic material that appeared to be responsible for bacterial adhesion. Transmission electron microscopy of negatively stained (2% [wt./vol.] uranyl acetate), sulfur-grown T. thiooxidans revealed extensive membrane blebbing (sloughing of outer membrane vesicles) and the presence of approximately 100 nm sized sulfur particles adsorbed to membrane material surrounding individual bacteria. Sulfite-grown bacteria did not possess membrane blebs. The amphipathic nature of these outer membrane vesicles appear to be responsible for overcoming the hydrophobic barrier necessary for the growth of T. thiooxidans on elemental sulfur.

  20. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia

    PubMed Central

    Saha, Somen; Annear, Peter Leslie

    2015-01-01

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor. PMID:25685728

  1. Overcoming access barriers to health services through membership-based microfinance organizations: a review of evidence from South Asia.

    PubMed

    Saha, Somen; Annear, Peter Leslie

    2014-06-30

    It is a challenge for the poor to overcome the barriers to accessing health services. Membership-based microfinance with associated health programmes can improve health outcomes for the poor. This study reviewed the evidence published between 1993 and 2013 on the role of membership-based microfinance with associated health programmes in improving health outcomes for the poor in South Asia. A total of 661 papers were identified and 26 selected for inclusion, based on the relevance and rigour of the research methods. Of these 26, five were evidence reviews. Of the remaining 21 papers, 12 were from India, seven from Bangladesh, and one each from Sri Lanka and Indonesia. Three papers addressed more than one theme. Five key themes emerged from the review: (i) the impact of microfinance programmes on the social and economic situation of the poor; (ii) the impact of microfinance programmes on community health; (iii) the impact of integrated microfinance health programmes on raising client awareness; (iv) the impact of integrated microfinance health programmes on financing health care; and (v) the impact of integrated microfinance health programmes on affordable health-care products and services. The review provides new evidence on the pathways through which microfinance helps to improve population health and value for money for such programmes. Among countries with large populations in the informal sector, there is a strong case for policy-makers to support these groups in providing access to life-saving health care among the poor.

  2. A Social Constructionist Inquiry Study on the Lived Experiences of Educators with Dyslexia Overcoming Workplace Barriers and Increasing Their Capacity for Success

    ERIC Educational Resources Information Center

    Taylor, Kathryn R.

    2017-01-01

    The purpose of this qualitative research is to journey the lives of educators with dyslexia growing up as K-12 students, working in the K-12 educational environment, and the means by which those educators overcome workplace barriers as analyzed by three guidelines under the Universal Design for Learning (UDL) principle, multiple means of…

  3. miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair.

    PubMed

    Gaudet, Andrew D; Mandrekar-Colucci, Shweta; Hall, Jodie C E; Sweet, David R; Schmitt, Philipp J; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia; Popovich, Phillip G

    2016-08-10

    Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. Axon regeneration after spinal cord injury (SCI) fails due to neuron

  4. Sterically hindered complexes of platinum(II) with planar heterocyclic nitrogen donors. A novel complex with 1-methyl-cytosine has a spectrum of activity different from cisplatin and is able of overcoming acquired cisplatin resistance.

    PubMed

    Margiotta, Nicola; Natile, Giovanni; Capitelli, Francesco; Fanizzi, Francesco P; Boccarelli, Angelina; De Rinaldis, Pietro; Giordano, Domenico; Coluccia, Mauro

    2006-11-01

    A very interesting series of water soluble platinum compounds violating some of the classical structure-activity relationships, but still showing antitumor activity, was reported by Hollis and collaborators some 25 years ago [L.S. Hollis, A.R. Amundsenm, E.W. Stern. J. Med. Chem. 32 (1989) 128-136]. The compounds, having formula [PtClA(2)L](+) (A(2)=two monodentate or a bidentate amine, L=a secondary or tertiary amine or a N-donor heterocycle), were characterized by a positive charge and three non-labile N-donor ligands. We have extended the investigation to analogous compounds in which 2,9-dimethyl-1,10-phenanthroline has taken the place of the A(2) ligand(s) and L is 2-picoline (1), 6-amino-2-picoline (2), or 1-methyl-cytosine (3). The X-ray analysis of 2 has revealed a bow-like distortion of the phenanthroline plane, a sloping of the phenanthroline plane with respect to the coordination plane, and an overall shielding of the metallic core by the ortho substituents of the phenanthroline and pyridine ligands. In vitro grow inhibition assays have been performed on the most water soluble complex 3. The results indicate that this complex is characterized by a potent growth inhibitory activity with mean IC(50) value (in a panel of 11 human tumor cell lines) of 1.1 microM to be compared with a mean value of 3.8 microM for cisplatin. The same compound also appears to completely overcome the acquired cisplatin resistance stemming from reduced uptake or a multifocal mechanism, thus pointing to a mechanism of action distinctly different from that of cisplatin.

  5. “My hair or my health”: Overcoming Barriers to Physical Activity in African American women with a focus on hairstyle-related factors

    PubMed Central

    Huebschmann, Amy G.; Campbell, Lucille Johnson; Brown, Candace S.; Dunn, Andrea L.

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n=51) were AA women aged 19–73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from 11/2012 to 2/2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was “lack of money” (27%) and among non-exercisers was “lack of self-discipline” (57%). A hairstyle-related barrier of “sweating out my hairstyle,” was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier. PMID:26495938

  6. "My hair or my health:" Overcoming barriers to physical activity in African American women with a focus on hairstyle-related factors.

    PubMed

    Huebschmann, Amy G; Campbell, Lucille Johnson; Brown, Candace S; Dunn, Andrea L

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n = 51) were AA women aged 19-73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from November 2012 to February 2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was "lack of money" (27%) and among non-exercisers was "lack of self-discipline" (57%). A hairstyle-related barrier of "sweating out my hairstyle" was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier.

  7. Sterically crowded gallium amidinate complexes

    SciTech Connect

    Dagorne, S.; Jordan, R.F.; Young, V.G. Jr.

    1999-10-25

    The sterically crowded gallium amidinate complexes {l{underscore}brace}{sup t}BuC(NR{prime}){sub 2}{r{underscore}brace}GaX{sub 2} (X = Cl, Me, Et, CH{sub 2}Ph; R{prime} = {sup i}Pr, Cy, {sup t}Bu) have been synthesized in good yield. X-ray crystallographic analyses show that the steric interactions between the {sup t}Bu and R{prime} groups influence the R{prime}{single{underscore}bond}N{single{underscore}bond}Ga angle and the steric environment at gallium.

  8. What Are the Barriers Which Discourage 15-16 Year-Old Girls from Participating in Team Sports and How Can We Overcome Them?

    PubMed Central

    Wetton, Abigail R.; Jones, Angela R.; Pearce, Mark S.

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport. PMID:24073416

  9. What are the barriers which discourage 15-16 year-old girls from participating in team sports and how can we overcome them?

    PubMed

    Wetton, Abigail R; Radley, Rebecca; Jones, Angela R; Pearce, Mark S

    2013-01-01

    Given the clear benefits of regular physical activity (such as reduced risks of cardiovascular disease and obesity, as well as other benefits including those related to mental health), exploration of the reasons that adolescent girls give for not taking part in team sports may be particularly valuable for enhancing later rates of participation. We combined questionnaires (n = 60) and semistructured interviews (n = 6) to assess the barriers that prevent 15-16-year-old girls from participating in extracurricular team games and what can be done to overcome these barriers and improve physical activity levels. Four barriers became prominent as to why girls in this sample do not participate: Internal Factors, Existing Stereotypes, Other Hobbies and Teachers. Methods to overcome these barriers were identified; changing teachers' attitudes and shifting the media's focus away from male sport. Following the successful summer Olympics and Paralympics in the UK, and the resulting positive focus on some of the nation's female athletes, a shift in focus may be possible. However, this needs to be maintained to allow girls more opportunities, role models and motivation to participate in sport.

  10. Sustainable steric stabilization of colloidal titania nanoparticles

    NASA Astrophysics Data System (ADS)

    Elbasuney, Sherif

    2017-07-01

    A route to produce a stable colloidal suspension is essential if mono-dispersed particles are to be successfully synthesized, isolated, and used in subsequent nanocomposite manufacture. Dispersing nanoparticles in fluids was found to be an important approach for avoiding poor dispersion characteristics. However, there is still a great tendency for colloidal nanoparticles to flocculate over time. Steric stabilization can prevent coagulation by introducing a thick adsorbed organic layer which constitutes a significant steric barrier that can prevent the particle surfaces from coming into direct contact. One of the main features of hydrothermal synthesis technique is that it offers novel approaches for sustainable nanoparticle surface modification. This manuscript reports on the sustainable steric stabilization of titanium dioxide nanoparticles. Nanoparticle surface modification was performed via two main approaches including post-synthesis and in situ surface modification. The tuneable hydrothermal conditions (i.e. temperature, pressure, flow rates, and surfactant addition) were optimized to enable controlled steric stabilization in a continuous fashion. Effective post synthesis surface modification with organic ligand (dodecenyl succinic anhydride (DDSA)) was achieved; the optimum surface coating temperature was reported to be 180-240 °C to ensure DDSA ring opening and binding to titania nanoparticles. Organic-modified titania demonstrated complete change in surface properties from hydrophilic to hydrophobic and exhibited phase transfer from the aqueous phase to the organic phase. Exclusive surface modification in the reactor was found to be an effective approach; it demonstrated surfactant loading level 2.2 times that of post synthesis surface modification. Titania was also stabilized in aqueous media using poly acrylic acid (PAA) as polar polymeric dispersant. PAA-titania nanoparticles demonstrated a durable amorphous polymeric layer of 2 nm thickness. This

  11. Advocating for responsible oil and natural gas extraction policies; FracTracker as a mechanism for overcoming the barriers to scientific advocacy for academics and communities

    NASA Astrophysics Data System (ADS)

    Ferrar, K. J.; Malone, S.; Kelso, M.; Lenker, B.

    2013-12-01

    The inability to translate data to scientific information that can readily be incorporated by citizens into the public arena is an obstacle for science-based advocacy. This issue is particularly poignant for shale oil and natural gas development via hydraulic fracturing, as the issue has become highly politicized. Barriers to engaging in policy debate are different but highly related for community members and scientists. For citizens and interest groups, barriers including accessibility, public awareness and data presentation limit the motivation for community involvement in political interactions. To overcome such barriers, social researchers call for public engagement to move upstream and many call for a broad engagement of scientists in science-based advocacy. Furthermore surveys have shown that citizens, interest groups, and decision-makers share a broad desire for scientists to engage in environmental policy development. Regardless, scientists face a number of perceived barriers, with academics expressing the most resistance to overcoming the tension created by adherence to the scientific method and the need to engage with the broader society, described by Schneider (1990) as the 'double ethical bind'. For the scientific community the appeal of public dissemination of information beyond the scope of academic journals is limited for a number of reasons. Barriers include preservation of credibility, peer attitudes, training, and career trajectory. The result is a lack of translated information available to the public. This systematic analysis of the FracTracker platform provides an evaluation of where the features of the public engagement, GIS platform has been successful at overcoming these barriers to public dissemination, where the platform needs further development or is ill-suited to address these issues, and the development of FracTracker as an outlet for scientific researchers to engage with citizens. The analysis will also provide insight into what

  12. [How are Pediatric Hospitals in North-Rhine Westfalia Prepared to Overcome Language Barriers? A Pilot Study Exploring The Structural Quality of Inpatient Care].

    PubMed

    Langer, T; Zapf, T; Wirth, S; Meyer, B; Wiegand, A; Timmen, H; Gupta, S J; Schuster, S; Geraedts, M

    2017-07-01

    Background In Germany, 35% of all children are considered to have a "migration background", and in the state of North-Rhine-Westfalia 43%. Frequently, one or both parents of a patient with a migration background have limited German language proficiency. Communication barriers due to a language difference can have a negative impact on quality of care, patient safety and costs of care. In this study, we investigate how children's hospitals are prepared to meet the challenges associated with language barriers. Methods We surveyed all children's hospitals in the state of North-Rhine-Westfalia, Germany. The questionnaire was based on the "Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (CLAS)" and was adapted to circumstances in Germany. Results Thirty-eight hospitals participated (51%) in this survey. Language barriers occurred frequently (75% of respondents mentioned language difficulties in more than 10% of the patient population). 82% of respondents rated their hospital to be "less than well prepared" to overcome language barriers. In the majority of hospitals (62%), the need for an interpreter was determined on a case-to-case basis and not according to any set protocol. In most cases bilingual staff was used for interpreting. However, only 38% of respondents found a list of available bilingual staff to be a sufficient resource. 42% of respondents did not know the monthly costs for professional interpreting services. In the remaining cases, costs were less than € 500/month. Conclusion To overcome language barriers, hospitals rely on local resources. The majority of respondents did not find them to be appropriate and sufficient. The development of quality standards and the provision of financial resources are necessary to mobilize this potential for improvement. Therefore, other disciplines and sectors of healthcare need to be analyzed in order to provide the evidence for a constructive discussion with decision makers in

  13. Strategies to Overcome Barriers to Implementation of Alcohol Screening and Brief Intervention in General Practice: a Delphi Study Among Healthcare Professionals and Addiction Prevention Experts.

    PubMed

    Abidi, L; Oenema, A; Nilsen, P; Anderson, P; van de Mheen, D

    2016-08-01

    Despite the evidence base, alcohol screening and brief intervention (ASBI) have rarely been integrated into routine clinical practice. The aim of this study is to identify strategies that could tackle barriers to ASBI implementation in general practice by involving primary healthcare professionals and addiction prevention experts. A three-round online Delphi study was carried out in the Netherlands. The first-round questionnaire consisted of open-ended questions to generate ideas about strategies to overcome barriers. In the second round, participants were asked to indicate how applicable they found each strategy. Items without consensus were systematically fed back with group median ratings and interquartile range (IQR) scores in the third-round questionnaire. In total, 39 out of 69 (57 %) invited participants enrolled in the first round, 214 participants completed the second round, and 144 of these (67 %) completed the third-round questionnaire. Results show that participants reached consensus on 59 of 81 strategies, such as the following: (1) use of E-learning technology, (2) symptom-specific screening by general practitioners (GPs) and/or universal screening by practice nurses, (3) reimbursement incentives, (4) supportive materials, (5) clear guidelines, (6) service provision of addiction care centers, and (7) more publicity in the media. This exploratory study identified a broad set of strategies that could potentially be used for overcoming barriers to ASBI implementation in general practice and paves the way for future research to experimentally test the identified implementation strategies using multifaceted approaches.

  14. The relative effectiveness of practice change interventions in overcoming common barriers to change: a survey of 14 hospitals with experience implementing evidence-based guidelines.

    PubMed

    Simpson, Fiona; Doig, Gordon S

    2007-10-01

    Changing practice to reflect current best evidence can be costly and time-consuming. The purpose of this survey was to determine the optimal combination of practice change interventions needed to overcome barriers to practice change commonly encountered in the intensive care unit (ICU). A survey instrument delivered by mail with email follow-up reminders. Fourteen hospitals throughout Australia and New Zealand. Individuals responsible for implementing an evidence-based guideline for nutritional support in the ICU. Practice change interventions were ranked in order of effectiveness and barriers to change were ranked in order of how frequently they were encountered. A response rate of 100% was achieved. Interventions traditionally regarded as strong (academic detailing, active reminders) were ranked higher than those traditionally regarded as moderate (audit and feedback), or weak (posters, mouse mats). The high ranks of the site initiation visit (educational outreach, modest) and in-servicing (didactic lectures, weak) were unexpected, as was the relatively low rank of educationally influential, peer-nominated opinion leaders. Four hospitals reported the same doctor-related barrier as 'most common' and the remaining 10 hospitals reported three different doctor-related barriers, two nursing-related barriers and three organizational barriers as most common. When designing a multifaceted, multi-centre change strategy, the selection of individual practice change interventions should be based on: (1) an assessment of available resources; (2) recognition of the importance of different types of barriers to different sites; (3) the potential for combinations of interventions to have a synergistic effect on practice change, and (4) the potential for combinations of interventions to actually reduce workload.

  15. Community based saving groups: an innovative approach to overcome the financial and social barriers in health care seeking by the women in the rural remote communities of Pakistan.

    PubMed

    Shaikh, Babar Tasneem; Noorani, Qayyum; Abbas, Shazia

    2017-01-01

    In remote rural areas of Pakistan, access to the maternal, newborn and child health (MNCH) care provided by a skilled health provider is quite difficult. There are many reasons such as women's restricted social mobility, lack of education, disenfranchised in decision making and poverty. To overcome these barriers and impediments in district Chitral, which is the largest territory in terms of geography in province Khyber Pakhtunkhwa, local women of reproductive age, were mobilized to form the Community Based Saving Groups (CBSGs) at the village level. In these CBSGs, they pool-in their money, and then provide soft loans to the expecting mothers to meet the expenses of delivery. Simultaneously, young literate women were identified from the local communities; they were trained as Community Midwives (CMWs), using national MNCH curriculum, and later deployed in their respective villages within the district. This study captured their perceptions about the formation of CBSGs to overcome the financial and social barriers, and subsequent use of CMW services. A qualitative enquiry was conducted with the delivered mothers and their husbands through gender specific separate focus group discussions, with CBSG members and with non-members in four different sites of District Chitral. CBSG member women were far more aware on health issues. Information sought from these forums brought a noticeable change in the health seeking practices. Seeking care from a trained birth attendant in the community became easier. Women associated with the CBSGs as members, expressed an increased access to money for utilizing the CMW services, better awareness on MNCH issues, and empowerment to decide for seeking care. CBSG have been an instrumental platform for social networking, helping each other in other household matters. Women have started using the services of CMW and the CBSGs have actually helped them overcome the financial barriers in health care seeking. Moreover, the CBSGs became a medium

  16. "We Don't Want to Talk about That": Overcoming Barriers to Rural Aging Research and Interventions on Sensitive Topics

    ERIC Educational Resources Information Center

    Zanjani, Faika; Rowles, Graham D.

    2012-01-01

    Geographical, economic, social and cultural barriers to accessing services in rural areas are widely reported. Less widely discussed are dilemmas posed by individual and community reluctance to address sensitive health issues. This article, focusing on the highly sensitive area of mental health, and employing a participatory action approach,…

  17. Overcoming language barriers in the informed consent process: regulatory and compliance issues with the use of the "short form".

    PubMed

    Lad, Pramod M; Dahl, Rebecca

    2014-01-01

    Language barriers in the informed consent process can be a significant impediment when recruiting non-English speaking subjects into clinical research studies. Regulatory guidelines indicate that the short form procedure be utilized in such circumstances. In this paper, we examine some of the ambiguities in the regulatory framework, the resulting need for institutional policy guidelines, and compliance issues with the short form process.

  18. "We Don't Want to Talk about That": Overcoming Barriers to Rural Aging Research and Interventions on Sensitive Topics

    ERIC Educational Resources Information Center

    Zanjani, Faika; Rowles, Graham D.

    2012-01-01

    Geographical, economic, social and cultural barriers to accessing services in rural areas are widely reported. Less widely discussed are dilemmas posed by individual and community reluctance to address sensitive health issues. This article, focusing on the highly sensitive area of mental health, and employing a participatory action approach,…

  19. Overcoming barriers to effectiveness in a health care operational environment: building on the lessons of American industry.

    PubMed

    Zimmerer, L W; Zimmerer, T W; Yasin, M M

    1999-01-01

    Several of the manufacturing-based philosophies, techniques and tools, such as Total Quality Management (TQM), Continuous Improvement (CI), Business Process Reengineering (BPR) and Time-based Competition (TBC) have been successfully adapted for use within the service sector. Diverse service industries including airlines, insurance, food services and hospitality have increased customer satisfaction and performance through the use of the quality driven, manufacturing-based philosophies. This article explores the reasons for the limited success of TQM/CI, BPR, TBC and benchmarking within the health care industry. Sixteen barriers to change are identified, possible counter-measures to these barriers are outlined and two conceptual frameworks are offered as possible facilitators of change for the health care industry.

  20. Overcoming the Barriers to Self-Knowledge: Mindfulness as a Path to Seeing Yourself as You Really Are.

    PubMed

    Carlson, Erika N

    2013-03-01

    People's beliefs about their personality, or how they typically think, feel, and behave, correspond somewhat to objective accuracy criteria. Yet recent research has highlighted the fact that there are many blind spots in self-knowledge and that these blind spots can have fairly negative consequences. What can people do to improve self-knowledge? The current article suggests that the construct of mindfulness, defined as paying attention to one's current experience in a nonevaluative way, may serve as a path to self-knowledge. Specifically, mindfulness appears to directly address the two major barriers to self-knowledge: informational barriers (i.e., the quantity and quality of information people have about themselves) and motivational barriers (i.e., ego-protective motives that affect how people process information about themselves). This article reviews the available evidence supporting the hypothesis that mindfulness improves self-knowledge and outlines promising future directions that might firmly establish an empirical link between mindfulness and self-knowledge. © The Author(s) 2013.

  1. Overcoming Barriers to Family Planning through Integration: Perspectives of HIV-Positive Men in Nyanza Province, Kenya

    PubMed Central

    Steinfeld, Rachel L.; Newmann, Sara J.; Onono, Maricianah; Cohen, Craig R.; Bukusi, Elizabeth A.; Grossman, Daniel

    2013-01-01

    This study explored barriers to and facilitators of using family planning services among HIV-positive men in Nyanza Province, Kenya. From May to June 2010, in-depth interviews were conducted with 30 men receiving care at 15 HIV clinics. The key barriers to the use of family planning included concerns about side effects of contraceptives, lack of knowledge about contraceptive methods, myths and misconceptions including fear of infertility, structural barriers such as staffing shortages at HIV clinics, and a lack of male focus in family planning methods and service delivery. The integration of family planning into HIV clinics including family planning counseling and education was cited as an important strategy to improve family planning receptivity among men. Integrating family planning into HIV services is a promising strategy to facilitate male involvement in family planning. Integration needs to be rigorously evaluated in order to measure its impact on unmet need for contraception among HIV-positive women and their partners and assure that it is implemented in a manner that engages both men and women. PMID:23738057

  2. Being "chill" with teachers and "frozen" by peers in science: overcoming social and educational barriers in a learning community

    NASA Astrophysics Data System (ADS)

    Kim, Hannah; Scantlebury, Kathryn

    2013-09-01

    This forum discusses the issue of `othering' and how intersectionality is a useful analytical framework for understanding the students' immigrant experiences in, and out of, the science classroom. We use a feminist perspective to discuss Minjung's study because gender is a key aspect of one's identity other aspects such as race, religion, socio-economic status, and age have assumed a significant status in gender studies. Lastly we examine the supports and barriers that cliques can produce and propose the importance of building a learning community in the science classroom to engage all students.

  3. Do we need to overcome barriers to learning in the workplace for foundation trainees rotating in neurosurgery in order to improve training satisfaction?

    PubMed

    Phan, Pho Nh; Patel, Keyur; Bhavsar, Amar; Acharya, Vikas

    2016-01-01

    Junior doctors go through a challenging transition upon qualification; this repeats every time they start a rotation in a new department. Foundation level doctors (first 2 years postqualification) in neurosurgery are often new to the specialty and face various challenges that may result in significant workplace dissatisfaction. The neurosurgical environment is a clinically demanding area with a high volume of unwell patients and frequent emergencies - this poses various barriers to learning in the workplace for junior doctors. We identify a number of key barriers and review ideas that can be trialed in the department to overcome them. Through an evaluation of current suggestions in the literature, we propose that learning opportunities need to be made explicit to junior doctors in order to encourage them to participate as a member of the team. We consider ideas for adjustments to the induction program and the postgraduate medical curriculum to shift the focus from medical knowledge to improving confidence and clinical skills in newly qualified doctors. Despite being a powerful window for opportunistic learning, the daily ward round is unfortunately not maximized and needs to be more learner focused while maintaining efficiency and time consumption. Finally, we put forward the idea of an open forum where trainees can talk about their learning experiences, identify subjective barriers, and suggest solutions to senior doctors. This would be achieved through departmental faculty development. These interventions are presented within the context of the neurosurgical ward; however, they are transferable and can be adapted in other specialties and departments.

  4. Overcoming barriers to effective early parenting interventions for attention-deficit hyperactivity disorder (ADHD): parent and practitioner views.

    PubMed

    Smith, E; Koerting, J; Latter, S; Knowles, M M; McCann, D C; Thompson, M; Sonuga-Barke, E J

    2015-01-01

    The importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low 'take-up' and high 'drop-out' rates compromise the effectiveness of such programmes within the community. This qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. Many of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented. © 2014 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.

  5. Using community-based participatory research to identify potential interventions to overcome barriers to adolescents’ healthy eating and physical activity

    PubMed Central

    Goh, Ying-Ying; Sipple-Asher, Bessie Ko; Uyeda, Kimberly; Hawes-Dawson, Jennifer; Olarita-Dhungana, Josephina; Ryan, Gery W.; Schuster, Mark A.

    2010-01-01

    Using a community-based participatory research approach, we explored adolescent, parent, and community stakeholder perspectives on barriers to healthy eating and physical activity, and intervention ideas to address adolescent obesity. We conducted 14 adolescent focus groups (n = 119), 8 parent focus groups (n = 63), and 28 interviews with community members (i.e., local experts knowledgeable about youth nutrition and physical activity). Participants described ecological and psychosocial barriers in neighborhoods (e.g., lack of accessible nutritious food), in schools (e.g., poor quality of physical education), at home (e.g., sedentary lifestyle), and at the individual level (e.g., lack of nutrition knowledge). Participants proposed interventions such as nutrition classes for families, addition of healthy school food options that appeal to students, and non-competitive physical education activities. Participants supported health education delivered by students. Findings demonstrate that community-based participatory research is useful for revealing potentially feasible interventions that are acceptable to community members. PMID:19544091

  6. Overcoming barriers to effective early parenting interventions for attention-deficit hyperactivity disorder (ADHD): parent and practitioner views

    PubMed Central

    Smith, E; Koerting, J; Latter, S; Knowles, M M; McCann, D C; Thompson, M; Sonuga-Barke, E J

    2015-01-01

    Background The importance of early intervention approaches for the treatment of attention-deficit hyperactivity disorder (ADHD) has been increasingly acknowledged. Parenting programmes (PPs) are recommended for use with preschool children with ADHD. However, low ‘take-up’ and high ‘drop-out’ rates compromise the effectiveness of such programmes within the community. Methods This qualitative study examined the views of 25 parents and 18 practitioners regarding currently available PPs for preschool children with ADHD-type problems in the UK. Semi-structured interviews were undertaken to identify both barriers and facilitators associated with programme access, programme effectiveness, and continued engagement. Results and conclusions Many of the themes mirrored previous accounts relating to generic PPs for disruptive behaviour problems. There were also a number of ADHD-specific themes. Enhancing parental motivation to change parenting practice and providing an intervention that addresses the parents' own needs (e.g. in relation to self-confidence, depression or parental ADHD), in addition to those of the child, were considered of particular importance. Comparisons between the views of parents and practitioners highlighted a need to increase awareness of parental psychological barriers among practitioners and for better programme advertising generally. Clinical implications and specific recommendations drawn from these findings are discussed and presented. PMID:24814640

  7. Exploring the role of social interactions and supports in overcoming accessibility barriers while undertaking health tours in India.

    PubMed

    Jana, Arnab; Harata, Noboru; Kiyoshi, Takami; Ohmori, Nobuaki

    2014-01-01

    This article explores the phenomenon of companionship as an adaptation strategy to counter the existing barriers to health care access in developing nations. Companionship is argued to be an outcome of "inter" and "intra" household collaboration to offer diverse supports in addition to altruism. The analysis of the household survey conducted in West Bengal, India, exhibited different patterns of health care tours and the associated dependencies. In addition to support in terms of mobility while traveling and companionship while waiting for the opportunity, support in terms of refuge is also found to be essential, especially for the poor while they undertake regional tours. Causal models focusing on aggregated general health tours and specific regional tours were estimated separately to comprehend the implicit social interactions and their effects on the patient as well as the companions. The research demonstrated that accessibility barriers affect not only the ill, but also those associated with them and at times adversely. Segregation of regional tours illustrated the gaps, which instigated such tours and also might aid in health infrastructure planning as a whole.

  8. The Value of Companion Diagnostics: Overcoming Access Barriers to Transform Personalised Health Care into an Affordable Reality in Europe.

    PubMed

    Wurcel, Victoria; Perche, Olivier; Lesteven, Daniel; Williams, Doris-Ann; Schäfer, Birgit; Hopley, Colin; Jungwirth, Rebecca; Postulka, Anne; Pasmans, Raf; Hermansson, Lisse-Lotte; Ott, Markus; Glorioso, Valeria

    2016-01-01

    Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access

  9. A Collaborative Care Telemedicine Intervention to Overcome Treatment Barriers for Latina Women with Depression during the Perinatal Period

    PubMed Central

    Baker-Ericzén, Mary J.; Connelly, Cynthia D.; Hazen, Andrea L.; Dueñas, Cecilia; Landsverk, John A.; Horwitz, Sarah McCue

    2013-01-01

    Maternal depression is highly prevalent (10 to 20%) during the perinatal period with rates as high as 35 to 40% for Latinas. However, few Latinas are either identified or treated during the perinatal period. To address these disparities, the Perinatal Mental Health Model (PMH) was designed to ameliorate the barriers that prevent adequate diagnoses and intervention. The PMH is a culturally sensitive, short-term telemedicine, and collaborative care intervention for addressing depression among Mexican American mothers. It attends to sociocultural and socioeconomic dimensions and is delivered by trained mental health advisors within obstetric care settings. This article describes the feasibility and acceptability of utilizing the PMH. Participants (n=79) were selected from a first year ongoing randomized trial in community obstetric clinics. The intervention seems feasible and acceptable; low-income Latinas, identified as depressed during the perinatal period, reported having access to a range of appropriate community services and high satisfaction. PMID:22709321

  10. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer.

    PubMed

    Davis, Ruth J; Van Waes, Carter; Allen, Clint T

    2016-07-01

    A significant subset of head and neck cancers display a T-cell inflamed phenotype, suggesting that patients with these tumors should respond to therapeutic approaches aimed at strengthening anti-tumor immune responses. A major barrier to the development of an effective anti-tumor immune response, at baseline or in response to immunotherapy, is the development of an immunosuppressive tumor microenvironment. Several well described mechanisms of effector immune cell suppression in the head and neck cancer microenvironment are discussed here, along with updates on current trials designed to translate what we have learned from pre-clinical and correlative clinical studies into improved responses in patients with head and neck cancer following immune activating therapies. Published by Elsevier Ltd.

  11. A collaborative care telemedicine intervention to overcome treatment barriers for Latina women with depression during the perinatal period.

    PubMed

    Baker-Ericzén, Mary J; Connelly, Cynthia D; Hazen, Andrea L; Dueñas, Cecilia; Landsverk, John A; Horwitz, Sarah McCue

    2012-09-01

    Maternal depression is highly prevalent (10-20%) during the perinatal period, with rates as high as 35% to 40% for Latinas. However, few Latinas are either identified or treated during the perinatal period. The Perinatal Mental Health (PMH) model was designed to ameliorate the barriers that prevent adequate diagnoses and intervention. The PMH is a culturally sensitive, short-term telemedicine, collaborative care intervention for addressing depression among Mexican American mothers. It attends to sociocultural and socioeconomic dimensions and is delivered by trained mental health advisors in obstetric care settings. This article describes the feasibility and acceptability of using the PMH. Participants (N = 79) were selected from a 1st-year ongoing randomized trial in community obstetric clinics. The intervention seems feasible and acceptable; low-income Latinas, identified as depressed during the perinatal period, reported having access to a range of appropriate community services and high satisfaction.

  12. Overcoming language and cultural barriers: a graphical communication tool to perform a parasitological screening in two vulnerable populations from Argentina.

    PubMed

    Buyayisqui, María Pía; Bordoni, Noemí; Garbossa, Graciela

    2013-01-01

    This is an exploratory study of the application of a support tool for the detection of asymptomatic subjects carrying enteric parasites in two vulnerable populations in Argentina: a shantytown in the city of Buenos Aires and a rural Wichí indigenous community in the province of Chaco. The ethnic and cultural diversity, high illiteracy rate, and language barriers called for the development of an auxiliary resource to explain stool sample collection procedures. In individual interviews with each family, the authors used two instructional guidance leaflets in comic strip format depicting the procedures. They evaluated the acceptance of the graphical communication tool on the basis of the number of retrieved samples. Percentages of respondent families were 72.2% and 66.7%, respectively. Definitive validation of these instruments would allow their use in community studies, community service learning experiences, and research on aboriginal communities that would otherwise be excluded from studies on health status.

  13. PLANET FORMATION IN STELLAR BINARIES. II. OVERCOMING THE FRAGMENTATION BARRIER IN α CENTAURI AND γ CEPHEI-LIKE SYSTEMS

    SciTech Connect

    Rafikov, Roman R.; Silsbee, Kedron

    2015-01-10

    Planet formation in small-separation (∼20 AU) eccentric binaries such as γ Cephei or α Centauri is believed to be adversely affected by the presence of the stellar companion. Strong dynamical excitation of planetesimals by the eccentric companion can result in collisional destruction (rather than growth) of 1-100 km objects, giving rise to the ''fragmentation barrier'' for planet formation. We revise this issue using a novel description of secular dynamics of planetesimals in binaries, which accounts for the gravity of the eccentric, coplanar protoplanetary disk, as well as gas drag. By studying planetesimal collision outcomes, we show, in contrast to many previous studies, that planetesimal growth and subsequent formation of planets (including gas giants) in AU-scale orbits within ∼20 AU separation binaries may be possible, provided that the protoplanetary disks are massive (≳ 10{sup –2} M {sub ☉}) and only weakly eccentric (disk eccentricity ≲ 0.01). These requirements are compatible with both the existence of massive (several M{sub J} ) planets in γ Cep-like systems and the results of recent simulations of gaseous disks in eccentric binaries. Terrestrial and Neptune-like planets can also form in lower-mass disks at small (sub-AU) radii. We find that the fragmentation barrier is less of a problem in eccentric disks that are apsidally aligned with the binary orbit. Alignment gives rise to special locations, where (1) relative planetesimal velocities are low and (2) the timescale of their drag-induced radial drift is long. This causes planetesimal pileup at such locations in the disk and promotes their growth locally, helping to alleviate the timescale problem for core formation.

  14. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds

    PubMed Central

    Elgar, Amelia T.; Freebody, Kylie; Pohlman, Catherine L.; Shoo, Luke P.; Catterall, Carla P.

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of “new forests” more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land. PMID:24904602

  15. Overcoming barriers to seedling regeneration during forest restoration on tropical pasture land and the potential value of woody weeds.

    PubMed

    Elgar, Amelia T; Freebody, Kylie; Pohlman, Catherine L; Shoo, Luke P; Catterall, Carla P

    2014-01-01

    Combating the legacy of deforestation on tropical biodiversity requires the conversion to forest of large areas of established pasture, where barriers to native plant regeneration include competition with pasture grasses and poor propagule supply (seed availability). In addition, initial woody plants that colonise pasture are often invasive, non-native species whose ecological roles and management in the context of forest regeneration are contested. In a restoration experiment at two 0.64 ha sites we quantified the response of native woody vegetation recruitment to (1) release from competition with introduced pasture grasses, and (2) local facilitation of frugivore-assisted seed dispersal provided by scattered woody plants and artificial bird perches. Herbicide pasture grass suppression during 20 months caused a significant but modest increase in density of native woody seedlings, together with abundant co-recruitment of the prominent non-native pioneer wild tobacco (Solanum mauritianum). Recruitment of native species was further enhanced by local structure in herbicide-treated areas, being consistently greater under live trees and dead non-native shrubs (herbicide-treated) than in open areas, and intermediate under bird perches. Native seedling recruitment comprised 28 species across 0.25 ha sampled but was dominated by two rainforest pioneers (Homalanthus novoguineensis, Polyscias murrayi). These early results are consistent with the expected increase in woody vegetation recruitment in response to release from competitive and dispersive barriers to rainforest regeneration. The findings highlight the need for a pragmatic consideration of the ecological roles of woody weeds and the potential roles of "new forests" more broadly in accelerating succession of humid tropical forest across large areas of retired agricultural land.

  16. Self-sampling for cervical screening: could it overcome some of the barriers to the Pap test?

    PubMed

    Mullins, Robyn; Scalzo, Katherine; Sultana, Farhana

    2014-12-01

    To determine which groups of women would be most likely to take part in self-sampling for cervical screening, and what they perceive as the key barriers and benefits to self-sampling. A random sample of 3000 women aged 18-69 in Victoria, Australia, were asked questions about "taking their own Pap test" in a telephone survey about cervical screening; 2526 answered the questions about self-sampling. The terminology "Pap test" was used in questions, due to the very low understanding of HPV and its link to cervical cancer. One-third of women (34.0%) indicated they would prefer to self-sample, 57.2% would not and 8.7% were unsure. Preference for self-sampling was significantly stronger among women who had not had a Pap test for more than three years (64.8%, p < .001) or who had never had one (62.1%, p < .001), compared with those up-to-date (27.0%). Convenience was a key benefit (37.8%), as was less embarrassment (31.5%). For those who did not want to self-sample or were unsure, key factors included professionals being more skilled (53.4% and 28.2% respectively), and doubts about being able to do it properly (28.9% and 23.6%). Self-sampling was most popular among women who needed to have a Pap test, and could potentially reach some women who are not participating appropriately in cervical screening. Key barriers to participation could be addressed by providing information about the test being for HPV, and being easier to do properly than a Pap test. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

    PubMed

    Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

    2006-12-15

    The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

  18. Obtaining family consent for participation in Alzheimer’s research in a Cuban-American population: Strategies to overcome the barriers

    PubMed Central

    Williams, Christine L.; Tappen, Ruth; Buscemi, Charles; Rivera, Richard; Lezcano, Jennifer

    2007-01-01

    Cultural values and beliefs affect family attitudes toward participation in research. Significant resistance to allowing their elders with dementia to participate in clinical research was encountered in Cuban-American families. These families expressed concern about disturbing the elder’s comfort (tranquilidad) and solitude (soledad) Furthermore, most believed that intervention would be futile. Feelings of guilt associated with nursing home placement may have been exacerbated by the suggestion that active intervention could be effective. Strategies to overcome these barriers included reduced emphasis on the potential superiority of the intervention to be tested, reassurance that contact with research staff was usually appreciated by participants, arrangements to talk with the family as a group about the study, and increased use of Spanish-language consent forms. PMID:11398568

  19. The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government.

    PubMed

    Mergel, Ines

    2014-12-23

    Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House's Digital Government Strategy. The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called "Prizes and Challenges", encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen.

  20. The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

    PubMed Central

    2014-01-01

    Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen. PMID:25537314

  1. Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities

    PubMed Central

    Salihu, Hamisu M.; Wilson, Ronee E.; King, Lindsey M.; Marty, Phillip J.; Whiteman, Valerie E.

    2015-01-01

    Background: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. Methods: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. Results: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. Conclusions and Global Health Implications: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials. PMID:27621990

  2. Overcoming endosomal barrier by amphotericin B-loaded dual pH-responsive PDMA-b-PDPA micelleplexes for siRNA delivery.

    PubMed

    Yu, Haijun; Zou, Yonglong; Wang, Yiguang; Huang, Xiaonan; Huang, Gang; Sumer, Baran D; Boothman, David A; Gao, Jinming

    2011-11-22

    The endosomal barrier is a major bottleneck for the effective intracellular delivery of siRNA by nonviral nanocarriers. Here, we report a novel amphotericin B (AmB)-loaded, dual pH-responsive micelleplex platform for siRNA delivery. Micelles were self-assembled from poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PDMA-b-PDPA) diblock copolymers. At pH 7.4, AmB was loaded into the hydrophobic PDPA core, and siRNA was complexed with a positively charged PDMA shell to form the micelleplexes. After cellular uptake, the PDMA-b-PDPA/siRNA micelleplexes dissociated in early endosomes to release AmB. Live cell imaging studies demonstrated that released AmB significantly increased the ability of siRNA to overcome the endosomal barrier. Transfection studies showed that AmB-loaded micelleplexes resulted in significant increase in luciferase (Luc) knockdown efficiency over the AmB-free control. The enhanced Luc knockdown efficiency was abolished by bafilomycin A1, a vacuolar ATPase inhibitor that inhibits the acidification of the endocytic organelles. These data support the central hypothesis that membrane poration by AmB and increased endosomal swelling and membrane tension by a "proton sponge" polymer provided a synergistic strategy to disrupt endosomes for improved intracellular delivery of siRNA. © 2011 American Chemical Society

  3. Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening†

    PubMed Central

    Alcaraz, Jordi; Mori, Hidetoshi; Ghajar, Cyrus M.; Brownfield, Doug; Galgoczy, Roland; Bissell, Mina J.

    2013-01-01

    Collective cell invasion (CCI) through interstitial collagenous extracellular matrix (ECM) is crucial to the initial stages of branching morphogenesis, and a hallmark of tissue repair and dissemination of certain tumors. The collagenous ECM acts as a mechanical barrier against CCI. However, the physical nature of this barrier and how it is overcome by cells remains incompletely understood. To address these questions, we performed theoretical and experimental analysis of mammary epithelial branching morphogenesis in 3D type I collagen (collagen-I) gels. We found that the mechanical resistance of collagen-I is largely due to its elastic rather than its viscous properties. We also identified two strategies utilized by mammary epithelial cells that can independently minimize ECM mechanical resistance during CCI. First, cells adopt a narrow tube-like geometry during invasion, which minimizes the elastic opposition from the ECM as revealed by theoretical modeling of the most frequent invasive shapes and sizes. Second, the stiffness of the collagenous ECM is reduced at invasive fronts due to its degradation by matrix metalloproteinases (MMPs), as indicated by direct measurements of collagen-I microelasticity by atomic force microscopy. Molecular techniques further specified that the membrane-bound MMP14 mediates degradation of collagen-I at invasive fronts. Thus, our findings reveal that MMP14 is necessary to efficiently reduce the physical restraints imposed by collagen-I during branching morphogenesis, and help our overall understanding of how forces are balanced between cells and their surrounding ECM to maintain collective geometry and mechanical stability during CCI. PMID:21993836

  4. STERIC EFFECTS IN ALPHA-OLEFIN REACTIVITY

    DTIC Science & Technology

    successfully applied to alpha - olefins to correlate reaction rates with steric effects and to explain, in part, the difficulty of obtaining desirable polymers from these olefins ....Addition reactions to the double bond of a series of sterically-hindered alpha - olefins have been carried out. The kinetics of these reaction were...measured and the rates of reaction correlated with the steric effects present in the olefin . A theory known as "Newman’s rule of six" has been

  5. Increasing Rural Adults' Participation in Collegial Programs: Exemplary Programs. Proceedings of the Rural Action Conference "Programs and Activities to Overcome Barriers to Rural Adult Participation in Postsecondary Education" (Blacksburg, Virginia, June 1-3, 1987).

    ERIC Educational Resources Information Center

    Sullins, W. Robert, Ed.; And Others

    Approximately 85 educators from six states participated in a regional conference designed to showcase exemplary and collaborative programs to overcome many of the barriers faced by rural adults in pursuing higher education. After the keynote address, "The Role of Adult Learning in Revitalizing Rural Communities," by Cornelia Butler Flora, the…

  6. Do “trainee-centered ward rounds” help overcome barriers to learning and improve the learning satisfaction of junior doctors in the workplace?

    PubMed Central

    Acharya, Vikas; Reyahi, Amir; Amis, Samuel M; Mansour, Sami

    2015-01-01

    Ward rounds are widely considered an underutilized resource with regard to medical education, and therefore, a project was undertaken to assess if the initiation of “trainee-centered ward rounds” would help improve the confidence, knowledge acquisition, and workplace satisfaction of junior doctors in the clinical environment. Data were collated from junior doctors, registrar grade doctors, and consultants working in the delivery suite at Luton and Dunstable University Hospital in Luton over a 4-week period in March–April 2013. A review of the relevant literature was also undertaken. This pilot study found that despite the reservations around time constraints held by both junior and senior clinicians alike, feedback following the intervention was largely positive. The junior doctors enjoyed having a defined role and responsibility during the ward round and felt they benefited from their senior colleagues’ feedback. Both seniors and junior colleagues agreed that discussing learning objectives prior to commencing the round was beneficial and made the round more learner-orientated; this enabled maximal learner-focused outcomes to be addressed and met. The juniors were generally encouraged to participate more during the round and the consultants endeavored to narrate their decision-making, both were measures that led to greater satisfaction of both parties. This was in keeping with the concept of “Legitimate peripheral participation” as described by Lave and Wenger. Overall, trainee-centered ward rounds did appear to be effective in overcoming some of the traditional barriers to teaching in the ward environment, although further work to formalize and quantify these findings, as well as using greater sample sizes from different hospital departments and the inclusion of a control group, is needed. PMID:26508899

  7. Do "trainee-centered ward rounds" help overcome barriers to learning and improve the learning satisfaction of junior doctors in the workplace?

    PubMed

    Acharya, Vikas; Reyahi, Amir; Amis, Samuel M; Mansour, Sami

    2015-01-01

    Ward rounds are widely considered an underutilized resource with regard to medical education, and therefore, a project was undertaken to assess if the initiation of "trainee-centered ward rounds" would help improve the confidence, knowledge acquisition, and workplace satisfaction of junior doctors in the clinical environment. Data were collated from junior doctors, registrar grade doctors, and consultants working in the delivery suite at Luton and Dunstable University Hospital in Luton over a 4-week period in March-April 2013. A review of the relevant literature was also undertaken. This pilot study found that despite the reservations around time constraints held by both junior and senior clinicians alike, feedback following the intervention was largely positive. The junior doctors enjoyed having a defined role and responsibility during the ward round and felt they benefited from their senior colleagues' feedback. Both seniors and junior colleagues agreed that discussing learning objectives prior to commencing the round was beneficial and made the round more learner-orientated; this enabled maximal learner-focused outcomes to be addressed and met. The juniors were generally encouraged to participate more during the round and the consultants endeavored to narrate their decision-making, both were measures that led to greater satisfaction of both parties. This was in keeping with the concept of "Legitimate peripheral participation" as described by Lave and Wenger. Overall, trainee-centered ward rounds did appear to be effective in overcoming some of the traditional barriers to teaching in the ward environment, although further work to formalize and quantify these findings, as well as using greater sample sizes from different hospital departments and the inclusion of a control group, is needed.

  8. Overcoming psychosocial and developmental barriers to blood and marrow transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with chronic myelogenous leukemia.

    PubMed

    Khazal, Sajad; Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M

    2014-11-01

    Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

  9. Overcoming: a concept analysis.

    PubMed

    Brush, Barbara L; Kirk, Keri; Gultekin, Laura; Baiardi, Janet M

    2011-01-01

    Nurses often work with individuals and populations striving to improve or maintain the quality of their lives. Many, struggling from complex health and social problems, are challenged to surmount barriers to achieve this goal. The growing number of homeless families in the United States represent one such cohort. To develop an operational definition of overcoming and explicate its meaning, attributes, and characteristics as it relates to homeless families. Using the concept analysis method described by Walker and Avant, along with an extensive literature review, and sample cases pertaining to family homelessness, we delineated the defining attributes, antecedents, consequences, and empirical referents of the concept, overcoming. The results of this concept analysis, particularly the relationship of overcoming to family homelessness, provide guidance for further conceptualization and empirical testing, as well as for clinical practice. © 2011 Wiley Periodicals, Inc.

  10. The Effect of Initiatives to Overcome Language Barriers and Improve Attendance: A Cross-Sectional Analysis of Adherence in an Inner City Chronic Pain Clinic.

    PubMed

    Andreae, Michael H; White, Robert S; Chen, Kelly Yan; Nair, Singh; Hall, Charles; Shaparin, Naum

    2016-07-14

    Language barriers can prevent pain physicians and patients from forming meaningful rapport and drive health care disparities. Non-adherence with scheduled pain clinic appointments deprives patients with chronic pain of needed specialist care.

  11. A Change Agent's Facilitation Process for Overcoming the Barriers of ICT Adoption for Educational Administration--The Case of a Rural-Bangladesh Vocational Institution

    ERIC Educational Resources Information Center

    Khalid, Md. Saifuddin; Nyvang, Tom

    2014-01-01

    The factors influencing the use of information and communication technologies (ICT) as a professional and management tool outside the classroom have received little research attention. The two objectives of this research were: how do stakeholders of educational administration experience the barriers of ICT adoption, and how can they facilitate the…

  12. A Change Agent's Facilitation Process for Overcoming the Barriers of ICT Adoption for Educational Administration--The Case of a Rural-Bangladesh Vocational Institution

    ERIC Educational Resources Information Center

    Khalid, Md. Saifuddin; Nyvang, Tom

    2014-01-01

    The factors influencing the use of information and communication technologies (ICT) as a professional and management tool outside the classroom have received little research attention. The two objectives of this research were: how do stakeholders of educational administration experience the barriers of ICT adoption, and how can they facilitate the…

  13. You can teach an old dog new tricks: a qualitative analysis of how residents of senior living communities may use the web to overcome spatial and social barriers.

    PubMed

    Winstead, Vicki; Anderson, William A; Yost, Elizabeth A; Cotten, Shelia R; Warr, Amanda; Berkowsky, Ronald W

    2013-08-01

    For adults in senior living communities, information and communication technologies (ICTs) can be used to increase and expand communication for a population that is often spatially and socially separated from the general public. Using qualitative observational data from a longitudinal study of the impact of ICT usage on the quality of life among residents in assisted and independent living communities, the authors examine whether ICTs can mitigate the effects of social and spatial barriers. The authors find that ICTs have the potential to allow individuals to transcend social and spatial barriers, providing residents with the ability to maintain and enhance social networks as well as provide a greater sense of connection to the world at large.

  14. You Can Teach an Old Dog New Tricks: A Qualitative Analysis of How Residents of Senior Living Communities May Use the Web to Overcome Spatial and Social Barriers*

    PubMed Central

    Winstead, Vicki; Anderson, William A.; Yost, Elizabeth A.; Cotten, Shelia R.; Warr, Amanda; Berkowsky, Ronald W.

    2017-01-01

    For adults in senior living communities, information and communication technologies, (ICTs) can be used to increase and expand communication for a population that is often spatially and socially separated from the general public. Using qualitative observational data from a longitudinal study of the impact of ICT usage on the quality of life among residents in assisted and independent living communities, we examine whether ICTs can mitigate the effects of social and spatial barriers. We find that ICTs have the potential to allow individuals to transcend social and spatial barriers, providing residents with the ability to maintain and enhance social networks as well as provide a greater sense of connection to the world at large. PMID:25474761

  15. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

  16. A critical analysis on the rotation barriers in butane.

    PubMed

    Mo, Yirong

    2010-04-16

    As a textbook prototype for the introduction of steric hindrance in organic chemistry, the elucidation of the butane rotation barriers is fundamental for structural theory, and requires a consistent theoretical model to differentiate the steric and electronic effects. Here we employed the BLW method to probe the electronic (hyperconjugative) interactions. Results show that although there are stronger hyperconjugative interactions in the staggered anti and gauche conformers than the eclipsed structures, the energy curve and barriers are dominated by the steric repulsion.

  17. Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro.

    PubMed

    Gregori, Maria; Bertani, Daniela; Cazzaniga, Emanuela; Orlando, Antonina; Mauri, Michele; Bianchi, Alberto; Re, Francesca; Sesana, Silvia; Minniti, Stefania; Francolini, Maura; Cagnotto, Alfredo; Salmona, Mario; Nardo, Luca; Salerno, Domenico; Mantegazza, Francesco; Masserini, Massimo; Simonutti, Roberto

    2015-12-01

    In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Overcoming language barriers in healthcare: A protocol for investigating safe and effective communication when patients or clinicians use a second language.

    PubMed

    Meuter, Renata F I; Gallois, Cindy; Segalowitz, Norman S; Ryder, Andrew G; Hocking, Julia

    2015-09-10

    Miscommunication in the healthcare sector can be life-threatening. The rising number of migrant patients and foreign-trained staff means that communication errors between a healthcare practitioner and patient when one or both are speaking a second language are increasingly likely. However, there is limited research that addresses this issue systematically. This protocol outlines a hospital-based study examining interactions between healthcare practitioners and their patients who either share or do not share a first language. Of particular interest are the nature and efficacy of communication in language-discordant conversations, and the degree to which risk is communicated. Our aim is to understand language barriers and miscommunication that may occur in healthcare settings between patients and healthcare practitioners, especially where at least one of the speakers is using a second (weaker) language. Eighty individual interactions between patients and practitioners who speak either English or Chinese (Mandarin or Cantonese) as their first language will be video recorded in a range of in- and out-patient departments at three hospitals in the Metro South area of Brisbane, Australia. All participants will complete a language background questionnaire. Patients will also complete a short survey rating the effectiveness of the interaction. Recordings will be transcribed and submitted to both quantitative and qualitative analyses to determine elements of the language used that might be particularly problematic and the extent to which language concordance and discordance impacts on the quality of the patient-practitioner consultation. Understanding the role that language plays in creating barriers to healthcare is critical for healthcare systems that are experiencing an increasing range of culturally and linguistically diverse populations both amongst patients and practitioners. The data resulting from this study will inform policy and practical solutions for

  19. Ring-Closing Metathesis of Co2(CO)6-Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers.

    PubMed

    Danilkina, Natalia A; Lyapunova, Anna G; Khlebnikov, Alexander F; Starova, Galina L; Bräse, Stefan; Balova, Irina A

    2015-06-05

    The feasibility of ring-closing metathesis (RCM) as a synthetic entry to 10- and 11-membered dienediynes fused to a benzothiophene core was explored by experimental and theoretical investigations. An established sequence of iodocyclization of o-(buta-1,3-diynyl)thioanisoles followed by Sonogashira coupling to form diethynylbenzothiophenes was used to synthesize terminal benzothiophene-fused enediyne diolefins as substrates for RCM. Encountering an unexpected lack of reactivity of these substrates under standard RCM conditions, we applied DFT calculations to reveal that the underlying cause was a positive change in Gibbs free energy. The change in Gibbs free energy was also found to be positive for RCM of indole- and benzannulated terminal diolefins when affording smaller than 12-membered rings. We found that modification of the enediyne-diolefin substrate as the Co2(CO)6-alkyne complex allowed the target benzothiophene-fused 11-membered dienediyne to be obtained via RCM; the alkyne complexation strategy therefore provides one valid technique for overcoming challenges to macrocyclization of this kind.

  20. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways.

    PubMed

    Shearer, Morven C; Niclou, Simone P; Brown, David; Asher, Richard A; Holtmaat, Anthony J G D; Levine, Joel M; Verhaagen, Joost; Fawcett, James W

    2003-12-01

    Invading meningeal cells form a barrier to axon regeneration after damage to the spinal cord and other parts of the CNS, axons stopping at the interface between meningeal cells and astrocytes. Axon behavior was examined using an in vitro model of astrocyte/meningeal cell interfaces, created by plating aggregates of astrocytes and meningeal cells onto coverslips. At these interfaces growth of dorsal root ganglion axons attempting to grow from astrocytes to meningeal cells was blocked, but axons grew rapidly from meningeal cells onto astrocytes. Meningeal cells were examined for expression of axon growth inhibitory molecules, and found to express NG2, versican, and semaphorins 3A and 3C. Astrocytes express growth promoting molecules, including N-Cadherin, laminin, fibronectin, and tenascin-C. We treated cultures in various ways to attempt to promote axon growth across the inhibitory boundaries. Blockade of NG2 with antibody and blockade of neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to meningeal cells. Blockade of permissive molecules on astrocytes with N-Cadherin blocking peptide or anti beta-1 integrin had no effect. Manipulation of axonal signalling pathways also increased axon growth from astrocytes to meningeal cells. Increasing cAMP levels and inactivation of rho were both effective when the cultures were fixed in paraformaldehyde, demonstrating that their effect is on axons and not via effects on the glial cells.

  1. Adaptation to Ephemeral Habitat May Overcome Natural Barriers and Severe Habitat Fragmentation in a Fire-Dependent Species, the Bachman's Sparrow (Peucaea aestivalis)

    PubMed Central

    Cerame, Blain; Cox, James A.; Brumfield, Robb T.; Tucker, James W.; Taylor, Sabrina S.

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat. PMID:25180939

  2. To Grab and To Hold: Cultivating communal goals to overcome cultural and structural barriers in first generation college students' science interest.

    PubMed

    Allen, Jill M; Muragishi, Gregg A; Smith, Jessi L; Thoman, Dustin B; Brown, Elizabeth R

    2015-12-01

    Homogeneity within science limits creativity and discovery, and can feed into a perpetuating cycle of underrepresentation. From enhancing social justice to alleviating health and economic disadvantages, broadening participation in science is imperative. We focus here on first-generation students (FGS) and identify factors which grab and hold science interest among this underrepresented group. Might the culture and norms within science unintentionally limit FGS' participation? We argue that two distinct aspects of communal goals contribute to FGS' underrepresentation at different stages of the STEM pipeline: cultural perceptions of science as uncommunal (little emphasis on prosocial behavior and collaboration) and the uncommunal structure of STEM graduate education and training. Across 2 studies we investigated factors that catch (Study 1) and hold (Study 2) FGS' science interest. In Study 1, we find only when FGS believe that working in science will allow them to fulfill prosocial communal purpose goals are they more intrinsically interested in science. Yet, later in the pipeline science education devalues prosocial communal goals creating a structural mobility barrier among FGS. Study 2 found that FGS generally want to stay close to home instead of relocating to pursue a graduate education. For FGS (versus continuing-generation students), higher prosocial communal goal orientation significantly predicted lower residential mobility. We discuss implications for interventions to counteract the uncommunal science education and training culture to help improve access to FGS and other similarly situated underrepresented populations.

  3. Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy.

    PubMed

    Fernandes, Alinda R; Chari, Divya M

    2016-09-28

    Genetically engineered neural stem cell (NSC) transplant populations offer key benefits in regenerative neurology, for release of therapeutic biomolecules in ex vivo gene therapy. NSCs are 'hard-to-transfect' but amenable to 'magnetofection'. Despite the high clinical potential of this approach, the low and transient transfection associated with the large size of therapeutic DNA constructs is a critical barrier to translation. We demonstrate for the first time that DNA minicircles (small DNA vectors encoding essential gene expression components but devoid of a bacterial backbone, thereby reducing construct size versus conventional plasmids) deployed with magnetofection achieve the highest, safe non-viral DNA transfection levels (up to 54%) reported so far for primary NSCs. Minicircle-functionalized magnetic nanoparticle (MNP)-mediated gene delivery also resulted in sustained gene expression for up to four weeks. All daughter cell types of engineered NSCs (neurons, astrocytes and oligodendrocytes) were transfected (in contrast to conventional plasmids which usually yield transfected astrocytes only), offering advantages for targeted cell engineering. In addition to enhancing MNP functionality as gene delivery vectors, minicircle technology provides key benefits from safety/scale up perspectives. Therefore, we consider the proof-of-concept of fusion of technologies used here offers high potential as a clinically translatable genetic modification strategy for cell therapy.

  4. Adaptation to ephemeral habitat may overcome natural barriers and severe habitat fragmentation in a fire-dependent species, the Bachman's Sparrow (Peucaea aestivalis).

    PubMed

    Cerame, Blain; Cox, James A; Brumfield, Robb T; Tucker, James W; Taylor, Sabrina S

    2014-01-01

    Bachman's Sparrow (Peucaea aestivalis) is a fire-dependent species that has undergone range-wide population declines in recent decades. We examined genetic diversity in Bachman's Sparrows to determine whether natural barriers have led to distinct population units and to assess the effect of anthropogenic habitat loss and fragmentation. Genetic diversity was examined across the geographic range by genotyping 226 individuals at 18 microsatellite loci and sequencing 48 individuals at mitochondrial and nuclear genes. Multiple analyses consistently demonstrated little genetic structure and high levels of genetic variation, suggesting that populations are panmictic. Based on these genetic data, separate management units/subspecies designations or translocations to promote gene flow among fragmented populations do not appear to be necessary. Panmixia in Bachman's Sparrow may be a consequence of an historical range expansion and retraction. Alternatively, high vagility in Bachman's Sparrow may be an adaptation to the ephemeral, fire-mediated habitat that this species prefers. In recent times, high vagility also appears to have offset inbreeding and loss of genetic diversity in highly fragmented habitat.

  5. To Grab and To Hold: Cultivating communal goals to overcome cultural and structural barriers in first generation college students' science interest

    PubMed Central

    Allen, Jill M.; Muragishi, Gregg A.; Smith, Jessi L.; Thoman, Dustin B.; Brown, Elizabeth R.

    2015-01-01

    Homogeneity within science limits creativity and discovery, and can feed into a perpetuating cycle of underrepresentation. From enhancing social justice to alleviating health and economic disadvantages, broadening participation in science is imperative. We focus here on first-generation students (FGS) and identify factors which grab and hold science interest among this underrepresented group. Might the culture and norms within science unintentionally limit FGS' participation? We argue that two distinct aspects of communal goals contribute to FGS' underrepresentation at different stages of the STEM pipeline: cultural perceptions of science as uncommunal (little emphasis on prosocial behavior and collaboration) and the uncommunal structure of STEM graduate education and training. Across 2 studies we investigated factors that catch (Study 1) and hold (Study 2) FGS' science interest. In Study 1, we find only when FGS believe that working in science will allow them to fulfill prosocial communal purpose goals are they more intrinsically interested in science. Yet, later in the pipeline science education devalues prosocial communal goals creating a structural mobility barrier among FGS. Study 2 found that FGS generally want to stay close to home instead of relocating to pursue a graduate education. For FGS (versus continuing-generation students), higher prosocial communal goal orientation significantly predicted lower residential mobility. We discuss implications for interventions to counteract the uncommunal science education and training culture to help improve access to FGS and other similarly situated underrepresented populations. PMID:26807431

  6. Mouse-adapted scrapie strains 139A and ME7 overcome species barrier to induce experimental scrapie in hamsters and changed their pathogenic features.

    PubMed

    Shi, Qi; Zhang, Bao-Yun; Gao, Chen; Zhang, Jin; Jiang, Hui-Ying; Chen, Cao; Han, Jun; Dong, Xiao-Ping

    2012-03-09

    Transmissible spongiform encephalopathy (TSE) diseases are known to be zoonotic diseases that can infect different kinds of animals. The transmissibility of TSE, like that of other infectious diseases, shows marked species barrier, either being unable to infect heterologous species or difficult to form transmission experimentally. The similarity of the amino acid sequences of PrP among species is believed to be one of the elements in controlling the transmission TSE interspecies. Other factors, such as prion strains and host's microenvironment, may also participate in the process. Two mouse-adapted strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of scrapie associate fibril (SAF) and PrPSc in brains of the infected animals were tested by TEM assays and Western blots dynamically during the incubation periods. The pathogenic features of the novel prions in hamsters, including electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase K-resistances and conformational stabilities were comparatively evaluated. TSE-related neuropathological changes were assayed by histological examinations. After long incubation times, mouse-adapted agents 139A and ME7 induced experimental scrapie in hamsters, respectively, showing obvious spongiform degeneration and PrPSc deposits in brains, especially in cortex regions. SAF and PrPSc in brains were observed much earlier than the onset of clinical symptoms. The molecular characteristics of the newly-formed PrPSc in hamsters, 139A-ha and ME7-ha, were obviously distinct from the original mouse agents, however, greatly similar as that of a hamster-adapted scrapie strain 263 K. Although the incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha were different, the pathogenic characteristics and neuropathological changes were highly similar. This finding concludes that mouse-adapted agents 139A and ME7 change their pathogenic characteristics during the transmission to

  7. Overcoming barriers to validation of non-animal partial replacement methods/Integrated Testing Strategies: the report of an EPAA-ECVAM workshop.

    PubMed

    Kinsner-Ovaskainen, Agnieszka; Akkan, Zerrin; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Dal Negro, Gianni; De Bruijn, Jack; De Silva, Odile; Gribaldo, Laura; Griesinger, Claudius; Jaworska, Joanna; Kreysa, Joachim; Maxwell, Gavin; McNamee, Pauline; Price, Anna; Prieto, Pilar; Schubert, Roland; Tosti, Luca; Worth, Andrew; Zuang, Valerie

    2009-09-01

    The use of Integrated Testing Strategies (ITS) in toxicological hazard identification and characterisation is becoming increasingly common as a method for enabling the integration of diverse types of toxicology data. At present, there are no existing procedures and guidelines for the construction and validation of ITS, so a joint EPAA WG5-ECVAM workshop was held with the following objectives: a) to investigate the role of ITS and the need for validation of ITS in the different industry sectors (pharmaceuticals, cosmetics, chemicals); b) to formulate a common definition of ITS applicable across different sectors; c) to explore how and when Three Rs methods are used within ITS; and d) to propose a validation rationale for ITS and for alternative methods that are foreseen to be used within ITS. The EPAA provided a platform for comparing experiences with ITS across different industry sectors. It became clear that every ITS has to be adapted to the product type, R&D stage, and regulatory context. However, common features of ITS were also identified, and this permitted the formulation of a general definition of ITS in a regulatory context. The definition served as a basis for discussing the needs, rationale and process of formal ITS validation. One of the main conclusions was that a formal validation should not be required, unless the strategy will serve as full replacement of an in vivo study used for regulatory purposes. Finally, several challenges and bottlenecks to the ITS validation were identified, and it was agreed that a roadmap on how to address these barriers would be established by the EPAA partners. 2009 FRAME.

  8. Enhanced clickability of doubly sterically-hindered aryl azides

    PubMed Central

    Yoshida, Suguru; Shiraishi, Akira; Kanno, Kimiyuki; Matsushita, Takeshi; Johmoto, Kohei; Uekusa, Hidehiro; Hosoya, Takamitsu

    2011-01-01

    Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group. Experimental and computational studies have indicated that the steric hindrance eliciting the inhibition of resonance between azido group and the aromatic ring is the primary cause of this apparently-paradoxical phenomenon. This is the first type of steric acceleration, indicating a possibility of designing a highly reactive functional group by strategically locating it in the sterically-congested environment. PMID:22355601

  9. Crystal structures of three sterically congested disilanes

    PubMed Central

    Pichaandi, Kothanda Rama

    2017-01-01

    In the three sterically congested silanes, C24H38Si2 (1) (1,1,2,2-tetra­isopropyl-1,2-di­phenyl­disilane), C24H34Br4Si2 (2) [1,1,2,2-tetra­kis­(2-bromo­propan-2-yl)-1,2-di­phenyl­disilane] and C32H38Si2 (3) (1,2-di-tert-butyl-1,1,2,2-tetra­phenyl­disilane), the Si—Si bond length is shortest in (1) and longest in (2), with (3) having an inter­mediate value, which parallels the increasing steric congestion. A comparison of the two isopropyl derivatives, (1 and 2), shows a significant increase in the Si—C(ipso) distance with the introduction of bromine. Also, in the brominated compound 2, attractive inter­molecular Br⋯Br inter­actions exist with Br⋯Br separations ca 0.52 Å shorter than the sum of the van der Waals radii. In compound 2, one of the bromo­isopropyl groups is rotationally disordered in an 0.8812 (9):0.1188 (9) ratio. Compound 3 exhibits ‘whole mol­ecule’ disorder in a 0.9645 (7):0.0355 (7) ratio with the Si—Si bonds in the two components making an angle of ca 66°. PMID:28316829

  10. Overcoming the Uncertainty Barrier to Adaptation

    EPA Pesticide Factsheets

    The second in a three-part webinar series about climate change adaptation for state and local governments, this webinar addressed the challenge of planning for climate change in the face of uncertainty.

  11. Overcoming the Adoption Barrier to Electric Flight

    NASA Technical Reports Server (NTRS)

    Borer, Nicholas K.; Nickol, Craig L.; Jones, Frank P.; Yasky, Richard J.; Woodham, Kurt; Fell, Jared S.; Litherland, Brandon L.; Loyselle, Patricia L.; Provenza, Andrew J.; Kohlman, Lee W.; hide

    2016-01-01

    Electrically-powered aircraft can enable dramatic increases in efficiency and reliability, reduced emissions, and reduced noise as compared to today's combustion-powered aircraft. This paper describes a novel flight demonstration concept that will enable the benefits of electric propulsion, while keeping the extraordinary convenience and utility of common fuels available at today's airports. A critical gap in airborne electric propulsion research is addressed by accommodating adoption at the integrated aircraft-airport systems level, using a confluence of innovative but proven concepts and technologies in power generation and electricity storage that need to reside only on the airframe. Technical discriminators of this demonstrator concept include (1) a novel, high-efficiency power system that utilizes advanced solid oxide fuel cells originally developed for ultra-long-endurance aircraft, coupled with (2) a high-efficiency, high-power electric propulsion system selected from mature products to reduce technical risk, assembled into (3) a modern, high-performance demonstration platform to provide useful and compelling data, both for the targeted early adopters and the eventual commercial market.

  12. Overcoming Learning Barriers through Knowledge Management

    ERIC Educational Resources Information Center

    Dror, Itiel E.; Makany, Tamas; Kemp, Jonathan

    2011-01-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and…

  13. Childhood lymphoedema and 'Lymphaletics': overcoming barriers.

    PubMed

    Todd, Marie

    2016-07-14

    Primary lymphoedema is a complex condition that causes tissue swelling, usually in one or more of the limbs, but lymphatic drainage of the head, trunk or deeper organs may also be affected. It can manifest in swelling at any time from birth meaning there are a number of children affected by this condition. While it is rare in childhood there are too few professionals experienced in diagnosis and treatment, which results in delays in identification and referral to appropriate services for diagnosis and treatment. The Children's Lymphoedema Special Interest Group (CLSIG) was formed in 2010 by a group of lymphoedema specialists in a bid to raise awareness, improve service provision, and enhance practitioner knowledge. One of the aims of the group was to deliver a 'fun day' (Lymphaletics) for children with lymphoedema and their families to encourage physical activity and social interaction with children who have similar problems, and to provide a source of parent-to-parent support. This article discusses the issues for children and their families, and the aims and format of the event.

  14. Overcoming the Uncertainty Barrier to Adaptation

    EPA Pesticide Factsheets

    The second in a three-part webinar series about climate change adaptation for state and local governments, this webinar addressed the challenge of planning for climate change in the face of uncertainty.

  15. Educating Women for Success: Overcoming Psychological Barriers.

    ERIC Educational Resources Information Center

    Stewart, Abigail J.

    1979-01-01

    Personal and institutional characteristics that might increase the likelihood of a female student successfully developing and pursuing individual goals are discussed. Three studies examine: psychological characteristics associated with life outcomes of satisfaction, effect of college education and environments on psychological characteristics, and…

  16. Overcoming Barriers to Shared Decision Making

    MedlinePlus

    ... second opinion . Learn more: About Advanced Heart Failure Recognition and Knowing Your Options Planning Ahead Communicating With ... Healthcare Team Help for Caregivers Advanced Heart Failure Recognition and Knowing Your Options Planning Ahead Communicating with ...

  17. Photon localization barrier can be overcome

    NASA Astrophysics Data System (ADS)

    Saari, P.; Menert, M.; Valtna, H.

    2005-02-01

    In contradistinction to a widespread belief that the spatial localization of photons is restricted by a power-law falloff of the photon energy density, Bialynicki-Birula [Phys. Rev. Lett. 80 (1998) 5247] has proved that any stronger - up to an almost exponential - falloff is allowed. We are showing that for certain specifically designed cylindrical one-photon states the localization is even better in lateral directions. If the photon state is built from the so-called focus wave mode, the falloff in the waist cross-section plane turns out to be quadratically exponential (Gaussian) and such strong localization persists in the course of propagation.

  18. Overcoming Disaster Barriers To Service All Children.

    ERIC Educational Resources Information Center

    Tramonte, Michael R.

    This paper contains an outline of a workshop designed for the disaster mental health worker. The goal of the workshop is to describe how disaster services are different from other mental health services and to provide suggestions on how to make these services more effective. The types of disasters, the anatomy of a disaster, and time phases of a…

  19. Overcoming Barriers to Classroom Technology Integration

    ERIC Educational Resources Information Center

    Kelly, Daniel P.

    2015-01-01

    Technology-savvy teachers are often the "go to" staff members in schools for their colleagues' technology issues. These teachers are seen as leaders within their schools with respect to technology and often do not understand their peers' difficulties when bringing technology into the classroom. Understanding both the reasons teachers may…

  20. Overcoming Barriers to Classroom Technology Integration

    ERIC Educational Resources Information Center

    Kelly, Daniel P.

    2015-01-01

    Technology-savvy teachers are often the "go to" staff members in schools for their colleagues' technology issues. These teachers are seen as leaders within their schools with respect to technology and often do not understand their peers' difficulties when bringing technology into the classroom. Understanding both the reasons teachers may…

  1. Overcoming Learning Barriers through Knowledge Management

    ERIC Educational Resources Information Center

    Dror, Itiel E.; Makany, Tamas; Kemp, Jonathan

    2011-01-01

    The ability to learn highly depends on how knowledge is managed. Specifically, different techniques for note-taking utilize different cognitive processes and strategies. In this paper, we compared dyslexic and control participants when using linear and non-linear note-taking. All our participants were professionals working in the banking and…

  2. Overcoming language barriers when teaching interprofessional groups.

    PubMed

    Welsh, Jeanette

    2012-10-01

    The author of this article undertook a small qualitative study of the best way to prepare unscheduled care staff for team-based delivery of patient care. The study was intended to highlight problems in interprofessional training courses so that guidelines for the delivery of such courses can be developed. The findings show that trainers cannot assume that all participants in training courses understand the terminology used. This article discusses this finding further.

  3. Overcoming Barriers to Progress in Exercise Genomics

    PubMed Central

    Bouchard, Claude

    2011-01-01

    This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. PMID:21697717

  4. Overcoming the Cutaneous Barrier with Microemulsions

    PubMed Central

    Lopes, Luciana B.

    2014-01-01

    Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

  5. Steric interactions between two grafted polymer brushes

    NASA Astrophysics Data System (ADS)

    Ruckenstein, Eli; Li, Buqiang

    1997-07-01

    A lattice model and a generator-matrix method are employed to calculate the interaction force profile between two grafted polymer brushes. The correlation between neighboring bonds and the interdigitation between the two brushes are taken into account. The calculations show that the effect of incorporating the bond correlations is equivalent to an increase in the value of the polymer-solvent interaction parameter when the bond correlations are ignored. The interdigitation between the two brushes decreases the free energy of the system and consequently results in a smaller steric repulsion. A complete interdigitation occurs at a separation close to half the separation between the two plates for which the interaction force is zero. The model is compared with the experimental interaction force profiles for ten systems which involve poly(2-vinylpyridine)-polyisoprene (PVP-PI), poly(2-vinylpyridine)-polystyrene (PVP-PS) block copolymers as well as end-functionalized polystyrenes (PS-X). For most of the systems, the theoretical predictions are in good agreement with experiment. In addition, the present results are compared with the equations proposed by de Gennes, based on the assumption of a step distribution function for the segment density, and by Milner et al., based on the parabolic distribution of the segment density. Both equations neglected interdigitation. It is shown in this paper that the interdigitation is not negligible and that it can decrease by an order of magnitude the repulsive force.

  6. From information theory to quantitative description of steric effects.

    PubMed

    Alipour, Mojtaba; Safari, Zahra

    2016-07-21

    Immense efforts have been made in the literature to apply the information theory descriptors for investigating the electronic structure theory of various systems. In the present study, the information theoretic quantities, such as Fisher information, Shannon entropy, Onicescu information energy, and Ghosh-Berkowitz-Parr entropy, have been used to present a quantitative description for one of the most widely used concepts in chemistry, namely the steric effects. Taking the experimental steric scales for the different compounds as benchmark sets, there are reasonable linear relationships between the experimental scales of the steric effects and theoretical values of steric energies calculated from information theory functionals. Perusing the results obtained from the information theoretic quantities with the two representations of electron density and shape function, the Shannon entropy has the best performance for the purpose. On the one hand, the usefulness of considering the contributions of functional groups steric energies and geometries, and on the other hand, dissecting the effects of both global and local information measures simultaneously have also been explored. Furthermore, the utility of the information functionals for the description of steric effects in several chemical transformations, such as electrophilic and nucleophilic reactions and host-guest chemistry, has been analyzed. The functionals of information theory correlate remarkably with the stability of systems and experimental scales. Overall, these findings show that the information theoretic quantities can be introduced as quantitative measures of steric effects and provide further evidences of the quality of information theory toward helping theoreticians and experimentalists to interpret different problems in real systems.

  7. Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro.

    PubMed

    Harper, G R; Davies, M C; Davis, S S; Tadros, T F; Taylor, D C; Irving, M P; Waters, J A

    1991-09-01

    Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.

  8. Dynamics of Azobenzene Dimer Photoisomerization: Electronic and Steric Effects.

    PubMed

    Titov, Evgenii; Granucci, Giovanni; Götze, Jan Philipp; Persico, Maurizio; Saalfrank, Peter

    2016-09-15

    While azobenzenes readily photoswitch in solution, their photoisomerization in densely packed self-assembled monolayers (SAMs) can be suppressed. Reasons for this can be steric hindrance and/or electronic quenching, e.g., by exciton coupling. We address these possibilities by means of nonadiabatic molecular dynamics with trajectory surface hopping calculations, investigating the trans → cis isomerization of azobenzene after excitation into the ππ* absorption band. We consider a free monomer, an isolated dimer and a dimer embedded in a SAM-like environment of additional azobenzene molecules, imitating in this way the gradual transition from an unconstrained over an electronically coupled to an electronically coupled and sterically hindered, molecular switch. Our simulations reveal that in comparison to the single molecule the quantum yield of the trans → cis photoisomerization is similar for the isolated dimer, but greatly reduced in the sterically constrained situation. Other implications of dimerization and steric constraints are also discussed.

  9. Density functional steric analysis of linear and branched alkanes.

    PubMed

    Ess, Daniel H; Liu, Shubin; De Proft, Frank

    2010-12-16

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (E(s)[ρ]), an electrostatic energy term (E(e)[ρ]), and a fermionic quantum energy term (E(q)[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes.

  10. Density Functional Steric Analysis of Linear and Branched Alkanes

    SciTech Connect

    Ess, Daniel H.; Liu, Shubin; De Proft, Frank

    2010-11-18

    Branched alkane hydrocarbons are thermodynamically more stable than straight-chain linear alkanes. This thermodynamic stability is also manifest in alkane bond separation energies. To understand the physical differences between branched and linear alkanes, we have utilized a novel density functional theory (DFT) definition of steric energy based on the Weizäcker kinetic energy. Using the M06-2X functional, the total DFT energy was partitioned into a steric energy term (Ee[[ρ]), an electrostatic energy term (Ee[ρ]), and a fermionic quantum energy term (Eq[[ρ]). This analysis revealed that branched alkanes have less (destabilizing) DFT steric energy than linear alkanes. The lower steric energy of branched alkanes is mitigated by an equal and opposite quantum energy term that contains the Pauli component of the kinetic energy and exchange-correlation energy. Because the steric and quantum energy terms cancel, this leaves the electrostatic energy term that favors alkane branching. Electrostatic effects, combined with correlation energy, explains why branched alkanes are more stable than linear alkanes.

  11. Overcoming: A Concept Analysis

    PubMed Central

    Brush, Barbara L.; Kirk, Keri; Gultekin, Laura; Baiardi, Janet M.

    2011-01-01

    This article provides an operational definition of overcoming as a first step in the systematic analysis of the concept. Using the method described by Walker and Avant (2005), the authors identify the attributes and characteristics of overcoming and its theoretical and practical application to nursing. Sample cases from clinical research illustrate the concept further. Further nursing research needs to test the theoretical relationships between overcoming and outcome variables. PMID:21806626

  12. STERIC FACTORS MODERATE CONFORMATIONAL FLUIDITY AND CONTRIBUTE TO THE HIGH PROTON SENSITIVITY OF ROOT EFFECT HEMOGLOBINS

    PubMed Central

    Bonaventura, Celia; Henkens, Robert; Friedman, Joel; Siburt, Claire J. Parker; Kraiter, Daniel; Crumbliss, Alvin L.

    2011-01-01

    The structural basis of the extreme pH dependence of oxygen binding to Root effect Hbs is a long-standing puzzle in the field of protein chemistry. A previously unappreciated role of steric factors in the Root effect was revealed by a comparison of pH effects on oxygenation and oxidation processes in human Hb relative to Spot (Leiostomus xanthurus) and Carp (Cyprinodon carpio) Hbs. The Root effect confers five-fold increased pH sensitivity to oxygenation of Spot and Carp Hbs relative to Hb A0 in the absence of anionic effectors, and even larger relative elevations of pH sensitivity of oxygenation in the presence of 0.2 M phosphate. Remarkably, the Root effect was not evident in the oxidation of the Root effect Hbs. This finding rules out pH-dependent alterations in the thermodynamic properties of the heme iron, measured in the anaerobic oxidation reaction, as the basis of the Root effect. The alternative explanation supported by these results is that the elevated pH sensitivity of oxygenation of Root effect Hbs is attributable to globin-dependent steric effects that alter oxygen affinity by constraining conformational fluidity, but which have little influence on electron exchange via the heme edge. This elegant mode of allosteric control can regulate oxygen affinity within a given quaternary state, in addition to modifying the T-R equilibrium. Evolution of Hb sequences that result in proton-linked steric barriers to heme oxygenation could provide a general mechanism to account for the appearance of the Root effect in the structurally diverse Hbs of many species. PMID:21745602

  13. Shock initiation sensitivity of PETN: A steric hindrance model

    SciTech Connect

    Dick, J.J.

    1991-01-01

    In this report, shock initiation sensitivity of PETN crystals is discussed. A new molecular model for shock sensitivity in crystalline solids is proposed in terms of steric hindrance to edge dislocation motion. This model is successful in predicting the relative shock sensitivities of the four PETN orientations studied, especially at low stresses. (JL)

  14. Sterically shielded diboron-containing metallocene olefin polymerization catalysts

    DOEpatents

    Marks, Tobin J.; Ja, Li; Yang, Xinmin

    1995-09-05

    A non-coordinating anion, preferably containing a sterically shielded diboron hydride, if combined with a cyclopenta-dienyl-substituted metallocene cation component, such as a zirconocene metallocene, is a useful olefin polymerization catalyst component. The anion preferably has the formula ##STR1## where R is branched lower alkyl, such as t-butyl.

  15. Origin of anomeric effect: A density functional steric analysis

    SciTech Connect

    Huang, Ying; Zhong, Ai-Guo; Yang, Qinsong; Liu, Shubin

    2011-01-01

    The anomeric effect (the tendency of heteroatomic substituents adjacent to a heteroatom within the cyclohexane ring to prefer the axial orientation instead of the sterically less hindered equatorial position) is traditionally explained through either the dipole moment repulsion or the hyperconjugation effect. In this work, by employing our recent work in density functional steric analysis, we provide a novel two-component explanation, which is consistent with the common belief in chemistry that the effect has a stereoelectronic origin. With α-D-glucopyranose as the prototype, we systematically explore its conformational space and generate 32 isomers, leading to a total of 80 axial–equatorial conformation pairs. The energy difference analysis of these pairs shows that while statistically speaking the tendency is valid, the anomeric effect is not always true and can be violated. Three energy components, exchange–correlation, classical electrostatic, and density functional steric, are found to be directly proportional to the total energy difference between axial and equatorial isomers. We also found that the total dipole moment change, not the hyperconjugation effect, is a reasonable indicator of the total energy difference. However, all these correlations alone are not strong enough to provide a compellingly convincing explanation for the general validity of the effect. With the help of strong correlations between energy components, an explanation with two energy components, steric and electrostatic, was proposed in this work. We show that the axial–equatorial energy difference in general, with the anomeric effect as a special case, is dictated by two factors of the stereoelectronic origin, steric hindrance and classical electrostaticinteractions, synchronously working together. Another explanation in terms of exchange–correlation and electrostaticinteractions has also been obtained in this work.

  16. Overcoming breastfeeding problems

    MedlinePlus

    Plugged milk ducts; Nipple soreness when breastfeeding; Breastfeeding - overcoming problems; Let-down reflex ... Breastfeeding (nursing) your baby can be a good experience for both the mother and the baby. It ...

  17. Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

    PubMed

    Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

    2016-04-19

    Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required

  18. Overcoming obstacles: collaboration for change.

    PubMed

    Funnell, M M

    2004-10-01

    Effective diabetes care requires a partnership between prepared, proactive practice teams and informed, activated patients. Diabetes education helps to overcome many of the barriers to effective self-management by enabling people with diabetes to make informed decisions about their day-to-day self-care. Both psychosocial and health outcomes have been improved through a variety of training programmes; however, education must be coupled with ongoing self-management support if these benefits are to be sustained. The principal goal of diabetes education has undergone a major shift over the past few years--evolving from primarily didactic interventions, focused on encouraging patients to adhere to the prescribed therapy, towards more interactive learning that supports people in making informed, self-directed decisions.

  19. Steric hindrances create a discrete linear Dy4 complex exhibiting SMM behaviour.

    PubMed

    Lin, Shuang-Yan; Zhao, Lang; Ke, Hongshan; Guo, Yun-Nan; Tang, Jinkui; Guo, Yang; Dou, Jianmin

    2012-03-21

    Two linear tetranuclear lanthanide complexes of general formula [Ln(4)(L)(2)(C(6)H(5)COO)(12)(MeOH)(4)], where HL = 2,6-bis((furan-2-ylmethylimino)methyl)-4-methylphenol, () and Ln(III) = Dy(III) (1) and Gd(III) (2), have been synthesized and characterized. The crystal structural analysis demonstrates that two Schiff-base ligands inhibit the growth of benzoate bridged 1D chains, leading to the isolation of discrete tetranuclear complexes due to their steric hindrances. Every Ln(III) ion is coordinated by eight donor atoms in a distorted bicapped trigonal-prismatic arrangement. Alternating current (ac) susceptibility measurements of complex 1 reveal a frequency- and temperature-dependent out-of-phase signal under zero dc field, typical of single-molecule magnet (SMM) behaviour with an anisotropic barrier Δ(eff) = 17.2 K.

  20. Overcoming recruitment barriers revealed high readiness to participate and low dropout rate among people with schizophrenia in a randomized controlled trial testing the effect of a Guided Self-Determination intervention

    PubMed Central

    2014-01-01

    Background Recruitment is one of the most serious challenges in performing randomized controlled trials. Often clinical trials with participants diagnosed with schizophrenia are terminated prematurely because of recruitment challenges resulting in a considerable waste of resources in the form of time, funding, and the participants’ efforts. Dropout rates in schizophrenia trials are also high. Recruitment challenges are often due to patients not wanting to participate in research but can also be due to clinicians’ concerns regarding individuals diagnosed with schizophrenia as participants in research. This paper reports how overcoming recruitment challenges not related to patients revealed high readiness to take part and low dropout rates in a one year long randomized controlled trial testing Guided Self-Determination (GSD) among outpatients with schizophrenia receiving treatment in Assertive Outreach Teams in the northern part of Denmark. Methods GSD is a shared decision-making and mutual problem-solving method using reflection sheets, which was developed in diabetes care and adjusted for this study and utilized by patients with schizophrenia. Descriptive data on strategies to overcome recruitment challenges were derived from notes and observations made during the randomized controlled trial testing of GSD in six outpatient teams. Results Three types of recruitment challenges not related to patients were identified and met during the trial: 1) organizational challenges, 2) challenges with finding eligible participants and 3) challenges with having professionals invite patients to participate. These challenges were overcome through: 1) extension of time, 2) expansion of the clinical recruitment area and 3) encouragement of professionals to invite patients to the study. Through overcoming these challenges, we identified a remarkably high patient-readiness to take part (101 of 120 asked accepted) and a low dropout rate (8%). Conclusion Distinction between

  1. Computational design of faster rotating second-generation light-driven molecular motors by control of steric effects.

    PubMed

    Oruganti, Baswanth; Fang, Changfeng; Durbeej, Bo

    2015-09-07

    We report a systematic computational investigation of the possibility to accelerate the rate-limiting thermal isomerizations of the rotary cycles of synthetic light-driven overcrowded alkene-based molecular motors through modulation of steric interactions. Choosing as a reference system a second-generation motor known to accomplish rotary motion in the MHz regime and using density functional theory methods, we propose a three-step mechanism for the thermal isomerizations of this motor and show that variation of the steric bulkiness of the substituent at the stereocenter can reduce the (already small) free-energy barrier of the rate-determining step by a further 15-17 kJ mol(-1). This finding holds promise for future motors of this kind to reach beyond the MHz regime. Furthermore, we demonstrate and explain why one particular step is kinetically favored by decreasing and another step is kinetically favored by increasing the steric bulkiness of this substituent, and identify a possible back reaction capable of impeding the rotary rate.

  2. Practical catalytic method for synthesis of sterically hindered anilines.

    PubMed

    Mailig, Melrose; Rucker, Richard P; Lalic, Gojko

    2015-07-14

    A practical catalytic method for the synthesis of sterically hindered anilines is described. The amination of aryl and heteroaryl boronic esters is accomplished using a catalyst prepared in situ from commercially available and air-stable copper(i) triflate and diphosphine ligand. For the first time, the method can be applied to the synthesis of both secondary and tertiary anilines in the presence of a wide range of functional groups. Esters, aldehydes, alcohols, aryl halides, ketones, nitriles, and nitro arenes are all compatible with the reaction conditions. Finally, even the most sterically hindered anilines can be successfully prepared under mild reaction conditions. Overall, the new method addresses significant practical limitations of a transformation previously developed in our lab, and provides a valuable complement to the existing methods for the synthesis of anilines.

  3. Interactions of triazine herbicides with biochar: Steric and electronic effects.

    PubMed

    Xiao, Feng; Pignatello, Joseph J

    2015-09-01

    We studied the adsorption of triazine herbicides and several reference heteroaromatic amines from water onto a temperature series of hardwood biochars (300-700 °C, labeled B300-B700). Adsorption on biochars correlated poorly with pyrolysis temperature, H/C, O/C, mean minimum fused ring size, surface area (N2 or CO2), microporosity, and mesoporosity, but correlated well with a weighted sum of microporosity and mesoporosity. Steric effects were evident by the negative influence of solute molecular volume on adsorption rate. For a given compound, adsorption rate maximized for the biochar with the greatest mesoporosity-to-total-porosity ratio, suggesting that mesopores are important for facilitating diffusion into pore networks. The cationic forms of amines adsorb more slowly than the neutral forms. To further probe steric and electronic effects, adsorption on a biochar (B400) was compared to adsorption on graphite-a nonporous reference material with an unhindered, unfunctionalized graphene surface-and in comparison with reference compounds (benzene, naphthalene, pyridine, quinoline and 1,3-triazine). Relative to benzene, the surface area-normalized adsorption of the triazine herbicides was disfavored on B400 (favored on graphite) by 11-19 kJ/mol, depending on concentration. It is estimated that steric suppression of B400 adsorption comprises 6.2 kJ/mol of this difference, the remainder being the difference in polar electronic effects. Based on the behavior of the reference amines, the difference in polar effects is dominated by π-π electron donor-acceptor (EDA) interactions with sites on polyaromatic surfaces, which are more electropositive and/or more abundant on graphite. Overall, our results show that mesoporosity is critical, that adsorption rate is a function of solute molecular size and charge, that steric bulk in the solute suppresses equilibrium adsorption, and that π-π EDA forces play a role in triazine polar interactions with biochar.

  4. Steric Effects in the Reaction of Aryl Radicals on Surfaces

    SciTech Connect

    Combellas, Catherine; Jiang, Deen; Kanoufi, Frederic; Pinson, Jean; Podvorica, Fetah

    2009-01-01

    Steric effects are investigated in the reaction of aryl radicals with surfaces. The electrochemical reduction of 2-, 3-, 4-methyl, 2-methoxy, 2-ethyl, 2,6-, 2,4-, and 3,5-dimethyl, 4-tert-butyl, 3,5-bis-tert-butyl benzenediazonium, 3,5-bis(trifluoromethyl), and pentafluoro benzenediazonium tetrafluoroborates is examined in acetonitrile solutions. It leads to the formation of grafted layers only if the steric hindrance at the 2- or 2,6-position(s) is small. When the 3,5-positions are crowded with tert-butyl groups, the growth of the organic layer is limited by steric effects and a monolayer is formed. The efficiency of the grafting process is assessed by cyclic voltammetry, X-ray photoelectron spectroscopy, infrared, and ellipsometry. These experiments, together with density functional computations of bonding energies of substituted phenyl groups on a copper surface, are discussed in terms of the reactivity of aryl radicals in the electrografting reaction and in the growth of the polyaryl layer.

  5. Overcoming Faculty Resistance.

    ERIC Educational Resources Information Center

    Gaff, Jerry G.

    1978-01-01

    Teaching improvement and institutional renewal efforts often face pessimism about change, if not suspicion and resistance, but faculty teams can overcome these problems through an action-oriented but low-profile "organic" approach. The need for personal invitations by colleagues is shown. (Author/LBH)

  6. Overcoming resistance to change.

    PubMed

    McKay, L

    1993-01-01

    The pace of change in health care organizations challenges nursing administrators at all levels of management to be effective change agents. As resistance is an inevitable element in the process of planned change, inclusion of interventions to overcome resistance is critical to the change agent role. The author presents five theoretically-based strategies for reducing the levels of resistance to planned change.

  7. Overcoming the Polyester Image.

    ERIC Educational Resources Information Center

    Regan, Dorothy

    1988-01-01

    Urges community colleges to overcome their image problem by documenting the colleges' impact on their communities. Suggests ways to determine what data should be collected, how to collect the information, and how it can be used to empower faculty, staff, and alumni to change the institution's image. (DMM)

  8. Rotational, steric, and coriolis effects on the F + HCl --> HF + Cl reaction on the 1(2)A' ground-state surface.

    PubMed

    Defazio, Paolo; Petrongolo, Carlo

    2009-04-23

    We present a quantum study of the reaction F((2)P) + HCl(X(1)Sigma(+)) --> HF(X(1)Sigma(+)) + Cl((2)P) on a recently computed 1(2)A' ground-state surface, considering HCl in the ground vibrational state, with up to 16 rotational quanta j(0). We employ the real wavepacket (WP) and flux methods for calculating coupled-channel (CC) and centrifugal-sudden (CS) initial-state probabilities up to J = 80 and 140, respectively. We also report CC and CS ground-state cross sections and CS excited-state cross sections and discuss the dynamics analyzing WP time evolutions. The HCl rotation highly enhances reaction probabilities and cross sections, as it was previously found for probabilities at J Steric effects favor indeed the overcoming of the potential barrier and a linearly dominated mechanism. Attractive Coriolis couplings favor instead the energy flow from the HCl rotation to the F-H---Cl reactive vibration. WP snapshots confirm and explain the HCl rotational effects, because the density into the nearly collinear F-H---Cl product channel increases remarkably with j(0). Finally, our CS rate constant is underestimated with respect to the experiment, pointing out the need of more accurate multisurface and CC calculations.

  9. Ion channel gates: comparative analysis of energy barriers.

    PubMed

    Tai, Kaihsu; Haider, Shozeb; Grottesi, Alessandro; Sansom, Mark S P

    2009-04-01

    The energetic profile of an ion translated along the axis of an ion channel should reveal whether the structure corresponds to a functionally open or closed state of the channel. In this study, we explore the combined use of Poisson-Boltzmann electrostatic calculations and evaluation of van der Waals interactions between ion and pore to provide an initial appraisal of the gating state of a channel. This approach is exemplified by its application to the bacterial inward rectifier potassium channel KirBac3.1, where it reveals the closed gate to be formed by a ring of leucine (L124) side chains. We have extended this analysis to a comparative survey of gating profiles, including model hydrophobic nanopores, the nicotinic acetylcholine receptor, and a number of potassium channel structures and models. This enables us to identify three gating regimes, and to show the limitation of this computationally inexpensive method. For a (closed) gate radius of 0.4 nm < R < 0.8 nm, a hydrophobic gate may be present. For a gate radius of 0.2 nm < R < 0.4 nm, both electrostatic and van der Waals interactions will contribute to the barrier height. Below R = 0.2 nm, repulsive van der Waals interactions are likely to dominate, resulting in a sterically occluded gate. In general, the method is more useful when the channel is wider; for narrower channels, the flexibility of the protein may allow otherwise-unsurmountable energetic barriers to be overcome.

  10. Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Stronach, M. W.; Ketner, R. J.; Hurley, T. B.

    1995-01-01

    Aliphatic amines react with phosphoimidazolide-activated derivatives of guanosine and cytidine (ImpN) by replacing the imidazole group. The kinetics of reaction of guanosine 5'-phospho-2-methylimidazolide (2-MeImpG) with glycine ethyl ester, glycinamide, 2-methoxyethylamine, n-butylamine, morpholine, dimethylamine (Me2NH), ethylmethylamine (EtNHMe), diethylamine (Et2NH), pyrrolidine, and piperidine were determined in water at 37 degrees C. With primary amines, a plot of the logarithm of the rate constant for attack by the amine on the protonated substrate, log kSH(A), versus the pKa of the amine exhibits a good linear correlation with a Bronsted slope, beta nuc = 0.48. Most of the secondary amines tested react with slightly higher reactivity than primary amines of similar pKa. Interestingly, some secondary amines show substantially lower reactivity than might be expected: EtNHMe reacts about eight times, and Et2NH at least 100 times, more slowly than Me2NH although all three amines are of similar basicity. For comparison, the kinetics of reaction of guanosine 5'-phosphoimidazolide (ImpG) and cytidine 5'-phosphoimidazolide (ImpC) were determined with Me2NH, EtNHMe, and Et2NH, and similar results were obtained. These results establish that the increased steric hindrance observed with the successive addition of ethyl groups are not due to any special steric requirements imposed by the guanosine or the methyl on the 2-methylimidazole leaving group of 2-MeImpG. It is concluded that addition of ethyl and, perhaps, groups larger than ethyl dramatically increases the kinetic barrier for addition of aliphatic secondary amines to the P-N bond of ImpN. This study supports the observation that the primary amino groups on the natural polyamines are at least 2 orders of magnitude more reactive than the secondary amino groups in the reaction with ImpN.

  11. Electrostatic and Steric Contributions to Block of the Skeletal Muscle Sodium Channel by μ-Conotoxin

    PubMed Central

    Hui, Kwokyin; Lipkind, Gregory; Fozzard, Harry A.; French, Robert J.

    2002-01-01

    Pore-blocking toxins are valuable probes of ion channels that underlie electrical signaling. To be effective inhibitors, they must show high affinity and specificity and prevent ion conduction. The 22-residue sea snail peptide, μ-conotoxin GIIIA, blocks the skeletal muscle sodium channel completely. Partially blocking peptides, derived by making single or paired amino acid substitutions in μ-conotoxin GIIIA, allow a novel analysis of blocking mechanisms. Replacement of one critical residue (Arg-13) yielded peptides that only partially blocked single-channel current. These derivatives, and others with simultaneous substitution of a second residue, were used to elucidate the structural basis of the toxin's blocking action. The charge at residue-13 was the most striking determinant. A positive charge was necessary, though not sufficient, for complete block. Blocking efficacy increased with increasing residue-13 side chain size, regardless of charge, suggesting a steric contribution to inhibition. Charges grouped on one side of the toxin molecule at positions 2, 12, and 14 had a weaker influence, whereas residue-16, on the opposite face of the toxin, was more influential. Most directly interpreted, the data suggest that one side of the toxin is masked by close apposition to a binding surface on the pore, whereas the other side, bearing Lys-16, is exposed to an aqueous cavity accessible to entering ions. Strong charge-dependent effects emanate from this toxin surface. In the native toxin, Arg-13 probably presents a strategically placed electrostatic barrier rather than effecting a complete steric occlusion of the pore. This differs from other well-described channel inhibitors such as the charybdotoxin family of potassium channel blockers and the sodium channel-blocking guanidinium toxins (tetrodotoxin and saxitoxin), which appear to occlude the narrow part of the pore. PMID:11773237

  12. Aluminum foils: the contrasting characters of hyperconjugation and steric repulsion in aluminum dimetallocenes.

    PubMed

    Compaan, Katherine R; Wilke, Jeremiah J; Schaefer, Henry F

    2011-08-31

    The novel sandwich complex Cp2*Al2I2, which was recently synthesized by Minasian and Arnold, has been characterized using ab initio and density functional methods. A large family of related compounds was also investigated. Although a few Al(II)–Al(II) bonds are known, this is the first such bond to be supported by Cp-type ligands. In addition, in the remarkable Cp4*Al4 synthesis by Roesky, Cp2*Al2I2 is the Al(II) intermediate; Cp4*Al4 is important as a precursor to novel organoaluminum species. Halogen and ligand effects on the Al–Al bond in Cp2*Al2I2 were systematically explored by studying a series of 20 Cp2*Al2I2 derivatives using density functional theory with relativistic basis sets for the halogens. Comparison was made with the focal point treatment, which uses extrapolation to estimate the full configuration interaction and complete basis set limit energy. Torsional potential energy curves, natural population analyses, and enthalpies of hydrogenation were computed. Using the focal point approach, torsional barriers were computed with 0.05 kcal mol(–1) uncertainty. The interplay of steric and electronic effects on the torsional potential energy curves, enthalpies of dehydrogenation reactions, and geometries is discussed. In species with small ligands (R = H, Me), hyperconjugative effects determine the torsional landscape, whereas steric repulsions dominate in species with Cp* alkyl ligands. Species with Cp ligands represent an intermediate case, thus providing insight into how ligands modulate the structures and properties of small metal clusters.

  13. Computational study of the effects of steric hindrance on amide bond cleavage.

    PubMed

    Matsubara, Toshiaki; Ueta, Chikako

    2014-09-25

    The reaction mechanism of amide bond cleavages of the 2,2,6,6-tetramethylpiperidine derivatives, which proceeds in methanol solvent under mild conditions, is examined by the density functional method (B3LYP) using a model substrate. We performed the calculations to clarify the reason why the amide bond is readily broken in the present system, on the basis of an experimentally proposed "proton switching pathway" that is different from the generally known mechanisms. As a result, it was found that the stepwise decomposition of the amide bond by the "proton switching pathway" significantly lowers the energy barrier. The delocalization of the π electron in the -C(═O)-N< part is hindered by the steric effect of the four Me groups of the piperidine so that the acetyl group can easily rotate around the C-N axis and then the α-H migrates to the amide N. The subsequent amide bond dissociation, which is thought to be a rate-determining step in the experiment, was very facile. The reaction is completed by the addition of methanol to the formed ketene. Both the energy barriers of the α-H migration to the amide N and the methanol addition to ketene are largely decreased by the mediation of methanol solvent molecules. The rate-determining step of the entire reaction was found to be the α-H migration.

  14. Thin Filament Structure and the Steric Blocking Model.

    PubMed

    Lehman, William

    2016-03-15

    By interacting with the troponin-tropomyosin complex on myofibrillar thin filaments, Ca2+ and myosin govern the regulatory switching processes influencing contractile activity of mammalian cardiac and skeletal muscles. A possible explanation of the roles played by Ca2+ and myosin emerged in the early 1970s when a compelling "steric model" began to gain traction as a likely mechanism accounting for muscle regulation. In its most simple form, the model holds that, under the control of Ca2+ binding to troponin and myosin binding to actin, tropomyosin strands running along thin filaments either block myosin-binding sites on actin when muscles are relaxed or move away from them when muscles are activated. Evidence for the steric model was initially based on interpretation of subtle changes observed in X-ray fiber diffraction patterns of intact skeletal muscle preparations. Over the past 25 years, electron microscopy coupled with three-dimensional reconstruction directly resolved thin filament organization under many experimental conditions and at increasingly higher resolution. At low-Ca2+, tropomyosin was shown to occupy a "blocked-state" position on the filament, and switched-on in a two-step process, involving first a movement of tropomyosin away from the majority of the myosin-binding site as Ca2+ binds to troponin and then a further movement to fully expose the site when small numbers of myosin heads bind to actin. In this contribution, basic information on Ca2+-regulation of muscle contraction is provided. A description is then given relating the voyage of discovery taken to arrive at the present understanding of the steric regulatory model. Copyright © 2016 John Wiley & Sons, Inc.

  15. Understanding the annual cycle in global steric height

    NASA Astrophysics Data System (ADS)

    Giglio, Donata; Roemmich, Dean; Cornuelle, Bruce

    2013-08-01

    Steric variability in the ocean includes diabatic changes in the surface layer due to air-sea buoyancy fluxes and adiabatic changes due to advection, which are dominant in the subsurface ocean. Here the annual signal in subsurface steric height (η'below 200 db) is computed on a global scale using temperature and salinity profiles from Argo floats. The zonal average of Δη' over a season (e.g., ηMarch'-ηDecember') is compared to the wind-forced vertical advection contribution (Δηw') both in the global ocean and in different basins. The results show agreement that extends beyond the tropics. The estimate of Δηw' is based on the Ekman pumping and assumes that the seasonal vertical velocity is constant over the depth range of interest. This assumption is consistent with annual isopycnal displacements inferred from Argo profiles. The contribution of horizontal advection to Δη'is significant in some regions and consistent with differences between Δη' and Δηw'.

  16. Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

    SciTech Connect

    Tomasello, Gaia; Altoe, Piero; Stenta, Marco; Olaso-Gonzalez, Gloria; Garavelli, Marco; Orlandi, Giorgio

    2007-12-26

    Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutral GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.

  17. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  18. Barriers to improvements in energy efficiency

    SciTech Connect

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  19. Lis1 regulates dynein by sterically blocking its mechanochemical cycle.

    PubMed

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-11-07

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein-Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the 'linker', from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle.

  20. Steric hindrance in a MnSalen expoxidation catalyst

    SciTech Connect

    Jun, K.W.; Wilson, R.B. Jr.; Asaro, M.F.

    1995-12-31

    Many transition metal epoxidation catalysts use porphyrin type ligands, as biomimetic models for the well-studied monooxygenase, Cyt P-450. Recently, non-porphyrin systems based on the Salen ligand have received attention, because high e.e. values are reported using chiral Salen ligands. These systems have yet to be rendered generally practical, however, because the catalyst lifetimes are very short and the turnover numbers low. The original Mn(III) Salen epoxidation catalysts became inactive within 1 h, showing only 5 to 10 turnovers. The modified, chiral Mn(III) Salen complexes show similarly low turnovers. The principal decomposition routes of the MnSalen epoxidation catalysts are not clear. The purpose of the present study is to determine whether incorporation of extreme steric hindrance into the Salen ligand could be used to increase the lifetime of the Mn(III) Salen epoxidation catalysts.

  1. Steric effects and preferential interactions in supercritical carbon dioxide

    SciTech Connect

    Saquing, C.D.; Lucien, F.P.; Foster, N.R

    1998-10-01

    Solubility data are presented for a mixture of o-hydroxybenzoic acid (o-HBA) and m-HBA in supercritical CO{sub 2} doped with 3.5 mol% methanol. The data were measured at 318 and 328 K and for pressures in the range of 101--201 bar. Some new data for the solubility of pure m-HBA in methanol-doped supercritical CO{sub 2} are also presented. The solubilities of the HBA isomers are enhanced considerably with the addition of methanol to supercritical CO{sub 2}. However, the solubility enhancement is strongly affected by the spatial arrangement of their functional groups (steric effect). There appears to be preferential interaction between the solutes and the cosolvent in the quaternary system, and this phenomenon is consistent with thermodynamic modeling of the system.

  2. Formation and collapse of gels of sterically stabilized colloidal particles

    NASA Astrophysics Data System (ADS)

    Weeks, James R.; van Duijneveldt, Jeroen S.; Vincent, Brian

    2000-11-01

    Colloidal silica spheres (diameter 88 nm) with a thick steric stabilization layer of polystyrene (PS; Mw = 26 600 g mol-1) were prepared. In cyclohexane, a marginal solvent for PS, particle aggregation and gelation were observed on lowering the temperature. Near the gelation temperature and at particle concentrations of a few per cent by weight, the gels were sufficiently weak to slowly compact under gravity. On quenching to slightly lower temperatures, the gels still settled, but the top of the sediment did not become flat, as is usually the case. This seems to be related to an unusual mechanism for gel compaction, which starts by forming a more dense structure at the top of the sample. It is proposed that this is related to the entangled polymer chains on neighbouring particles resisting substantial rearrangement of the local structure. The transient gelation phenomenon, observed previously for mixtures of colloid and non-adsorbing polymer, has so far not been observed for our system.

  3. Blocking cyclobutane pyrimidine dimer formation by steric hindrance.

    PubMed

    Vendrell-Criado, Victoria; Lhiaubet-Vallet, Virginie; Yamaji, Minoru; Cuquerella, M Consuelo; Miranda, Miguel A

    2016-04-26

    The efficiency of thymine (Thy) and uracil (Ura) to form cyclobutane pyrimidine dimers (CPDs) in solution, upon UV irradiation differs by one order of magnitude. This could to be partially related to the steric hindrance induced by the methyl at C5 in thymine. The aim of the present work is to establish the influence of a bulky moiety at this position on the photoreactivity of pyrimidines. With this purpose, photosensitization with benzophenone and acetone of a 5-tert-butyl uracil derivative () and the equivalent Thy () has been compared. Introduction of the tert-butyl group completely blocks CPD formation. Moreover, the mechanistic insight obtained by laser flash photolysis is in accordance with the observed photoreactivity.

  4. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    NASA Astrophysics Data System (ADS)

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

    2012-03-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  5. Sterically stabilized water based magnetic fluids: Synthesis, structure and properties

    NASA Astrophysics Data System (ADS)

    Bica, Doina; Vékás, Ladislau; Avdeev, Mikhail V.; Marinică, Oana; Socoliuc, Vlad; Bălăsoiu, Maria; Garamus, Vasil M.

    2007-04-01

    Magnetic fluids (MFs), prepared by chemical co-precipitation followed by double layer steric and electrostatic (combined) stabilization of magnetite nanoparticles dispersed in water, are presented. Several combinations of surfactants with different chain lengths (lauric acid (LA), myristic acid (MA), oleic acid (OA) and dodecyl-benzene-sulphonic acid (DBS)) were used, such as LA+LA, MA+MA, LA+DBS, MA+DBS, OA+DBS, OA+OA and DBS+DBS. Static light scattering, transmission electron microscopy, small angle neutron scattering, magnetic and magneto-rheological measurements revealed that MFs with MA+MA or LA+LA biocompatible double layer covered magnetite nanoparticles are the most stable colloidal systems among the investigated samples, and thus suitable for biomedical applications.

  6. Steric-electronic effects in malarial peptides inducing sterile immunity

    SciTech Connect

    Moreno-Vranich, Armando; Patarroyo, Manuel E.

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer Is it evident that the residues position are relevant regarding of {phi} angular value. Black-Right-Pointing-Pointer The geometry considered for detailing the alterations undergone by HABPs. Black-Right-Pointing-Pointer The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition, to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.

  7. Sterically Hindered Chiral Organometallic Complexes: AN X-Ray Crystallographic, NMR Spectroscopic and Ehmo Study.

    NASA Astrophysics Data System (ADS)

    Malisza, Krisztina Laura

    Sterically crowded organometallic complexes present fascinating problems of structure and molecular dynamics. Tetrahedral clusters such as (RCequivCR ^')rm(C_5H_5)_2M _2(CO)_4, where M = Mo or W, crystallize in conformations possessing three terminal carbonyls while the fourth is semi-bridging. However, these ligands undergo a rapid exchange process which can be followed by variable -temperature NMR spectroscopy. When the R substituent is derived from a chiral natural product, the low temperature NMR spectra reveal the presence of diastereomers which are interconvertible via rotations of the organometallic vertices. The fluxional behaviour of tetrahedral clusters containing such vertices as Co(CO)_3, Fe(CO)_3 or rm(C_5H _5)Mo(CO)_2 can be rationalized by means of molecular orbital calculations at the extended Huckel level of approximation. These studies show that the barriers to vertex rotation can usually be traced to one principal orbital interaction in each case. However, in rm(C_5H_5)_2Mo_2(CO) _4(R-CequivC-R) clusters, the barriers are primarily steric in character. The ability of transition metal clusters to delocalize electronic charge is well known and, in principle, could be used to stabilize intermediates of biochemical significance. Treatment of 2-methylcyclopentanone with an alkyne anion was carried out in order to generate 1-alkynyl-2-methylcyclopentanols in which the methyl and alkynyl groups are trans diaxial; the aim was to mimic the "D"-ring of the steroidal contraceptive mestranol. In fact, the major epimer was the one in which the methyl and alkynyl substituents were disposed in a cis manner. The conformation of 2-methyl-1-phenylethynylcyclopentanol 47 was elucidated by two-dimensional NMR techniques. Moreover, the structure of 47 and also of its rm Co _2(CO)_6 derivative have been determined crystallographically. Protonation of the dicobalt or dimolybdenum complexes of 47 lead to stable cations; treatment of these cations with nucleophiles

  8. The Role of Atomic Level Steric Effects and Attractive Forces in Protein Folding

    PubMed Central

    Lammert, Heiko; Wolynes, Peter G.; Onuchic, José N.

    2011-01-01

    Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the Cβ atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding however the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. PMID:22081451

  9. Psychological Barriers to Behavior Change

    PubMed Central

    Olson, James M.

    1992-01-01

    Adopting a healthy lifestyle often requires changing patterns of behavior. This article describes three categories of psychological barriers to behavior change: those that prevent the admission of a problem, those that interfere with initial attempts to change behavior, and those that make long-term change difficult. Strategies are identified that family physicians can use to overcome the barriers. PMID:21221258

  10. Highly durable photochromic radical complexes having no steric protections of radicals.

    PubMed

    Kobayashi, Yoichi; Mishima, Yasuhiro; Mutoh, Katsuya; Abe, Jiro

    2017-04-21

    Steric protection groups are usually necessary for stable radicals. However, here, we developed novel photochromic radical complexes which generate sterically unprotected imidazolyl and phenoxyl radicals upon UV light irradiation based on the phenoxyl-imidazolyl radical complex (PIC) framework. These photochromic compounds show excellent durability against repeated irradiation of intense nanosecond laser pulses even in polar protic solvents, such as ethanol.

  11. Azaphthalocyanines with fused triazolo rings: formation of sterically stressed constitutional isomers.

    PubMed

    Novakova, Veronika; Roh, Jaroslav; Gela, Petr; Kuneš, Jiří; Zimcik, Petr

    2012-05-07

    The presented work deals with synthesis and isolation of constitutional isomers of triazolo-fused azaphthalocyanines. Distribution of the isomers did not follow the statistical calculations due to steric effects of the substituents preferring the least sterically stressed C(4h) isomer.

  12. Geometrical features of hydrogen bonded complexes involving sterically hindered pyridines.

    PubMed

    Andreeva, Daria V; Ip, Brenda; Gurinov, Andrey A; Tolstoy, Peter M; Denisov, Gleb S; Shenderovich, Ilja G; Limbach, Hans-Heinrich

    2006-09-21

    The ability of strongly sterically hindered pyridines to form hydrogen bonded complexes was inspected using low-temperature 1H and 15N NMR spectroscopy in a liquefied Freon mixture. The proton acceptors were 2,6-di(tert-butyl)-4-methyl- and 2,6-di(tert-butyl)-4-diethylaminopyridine; the proton donors were hydrogen tetrafluoroborate, hydrogen chloride, and hydrogen fluoride. The presence of the tert-butyl groups in the ortho positions dramatically perturbed the geometry of the forming hydrogen bonds. As revealed by experiment, the studied crowded pyridines could form hydrogen bonded complexes with proton donors exclusively through their protonation. Even the strongest small proton acceptor, anion F-, could not be received by the protonated base. Instead, the simplest hydrogen bonded complex involved the [FHF]- anion. This complex was characterized by the shortest possible N...F distance of about 2.8 A. Because the ortho tert-butyl groups did not prevent the hydrogen bond interaction between the protonated center and the anion completely, an increase of the pyridine basicity caused a further shortening of the N-H distance and a weakening of the hydrogen bond to the counterion.

  13. Lis1 regulates dynein by sterically blocking its mechanochemical cycle

    PubMed Central

    Toropova, Katerina; Zou, Sirui; Roberts, Anthony J; Redwine, William B; Goodman, Brian S; Reck-Peterson, Samara L; Leschziner, Andres E

    2014-01-01

    Regulation of cytoplasmic dynein's motor activity is essential for diverse eukaryotic functions, including cell division, intracellular transport, and brain development. The dynein regulator Lis1 is known to keep dynein bound to microtubules; however, how this is accomplished mechanistically remains unknown. We have used three-dimensional electron microscopy, single-molecule imaging, biochemistry, and in vivo assays to help establish this mechanism. The three-dimensional structure of the dynein–Lis1 complex shows that binding of Lis1 to dynein's AAA+ ring sterically prevents dynein's main mechanical element, the ‘linker’, from completing its normal conformational cycle. Single-molecule experiments show that eliminating this block by shortening the linker to a point where it can physically bypass Lis1 renders single dynein motors insensitive to regulation by Lis1. Our data reveal that Lis1 keeps dynein in a persistent microtubule-bound state by directly blocking the progression of its mechanochemical cycle. DOI: http://dx.doi.org/10.7554/eLife.03372.001 PMID:25380312

  14. Sterically allowed configuration space for amino acid dipeptides

    NASA Astrophysics Data System (ADS)

    Caballero, Diego; Maatta, Jukka; Sammalkorpi, Maria; O'Hern, Corey; Regan, Lynne

    2014-03-01

    Despite recent improvements in computational methods for protein design, we still lack a quantitative, predictive understanding of the intrinsic propensities for amino acids to be in particular backbone or side-chain conformations. This question has remained unsettled for years because of the discrepancies between different experimental approaches. To address it, I performed all-atom hard-sphere simulations of hydrophobic residues with stereo-chemical constraints and non-attractive steric interactions between non-bonded atoms for ALA, ILE, LEU and VAL dipeptide mimetics. For these hard-sphere MD simulations, I show that transitions between α-helix and β-sheet structures only occur when the bond angle τ(N -Cα - C) >110° , and the probability distribution of bond angles for structures in the `bridge' region of ϕ- ψ space is shifted to larger angles compared to that in other regions. In contrast, the relevant bond-angle distributions obtained from most molecular dynamics packages are broader and shifter to larger values. I encounter similar correlations between bond angles and side-chain dihedral angles. The success of these studies is an argument for re-incorporating local stereochemical constraints into computational protein design methodology.

  15. Stereoisomers Probe Steric Zippers in Amyloid-β.

    PubMed

    Chandra, Bappaditya; Korn, Alexander; Maity, Barun Kumar; Adler, Juliane; Rawat, Anoop; Krueger, Martin; Huster, Daniel; Maiti, Sudipta

    2017-02-14

    Shape complementarity between close-packed residues plays a critical role in the amyloid aggregation process. Here, we probe such "steric zipper" interactions in amyloid-β (Aβ40), whose aggregation is linked to Alzheimer's disease, by replacing natural residues by their stereoisomers. Such mutations are expected to specifically destabilize the shape sensitive "packing" interactions, which may potentially increase their solubility and change other properties. We study the stereomutants DF19 and DL34 and also the DA2/DF4/DH6/DS8 mutant of Aβ40. F19-L34 is a critical contact in a tightly packed region of Aβ, while residues 1-9 are known to be disordered. While both DF19 and DL34 slow down the kinetics of aggregation and form amyloid fibrils efficiently, only DL34 increases the final solubility. DF19 gives rise to additional off-pathway aggregation which results in large, kinetically stable aggregates, and has lower net solubility. DA2/DF4/DH6/DS8 does not have an effect on the kinetics or the solubility. Notably, both DF19 and DL34 oligomers have a significantly lower level of interactions with lipid vesicles and live cells. We conclude that stereoisomers can cause complex site dependent changes in amyloid properties, and provide an effective tool to determine the role of individual residues in shaping the packed interiors of amyloid aggregates.

  16. Modulated nematic structures induced by chirality and steric polarization

    NASA Astrophysics Data System (ADS)

    Longa, Lech; PajÄ k, Grzegorz

    2016-04-01

    What kind of one-dimensional modulated nematic structures (ODMNS) can form nonchiral and chiral bent-core and dimeric materials? Here, using the Landau-de Gennes theory of nematics, extended to account for molecular steric polarization, we study a possibility of formation of ODMNS, both in nonchiral and intrinsically chiral liquid crystalline materials. Besides nematic and cholesteric phases, we find four bulk ODMNS for nonchiral materials, two of which, to the best of our knowledge, have not been reported so far. These two structures are longitudinal (NLP) and transverse (NTP) periodic waves where the polarization field being periodic in one dimension stays parallel and perpendicular, respectively, to the wave vector. The other two phases are the twist-bend nematic phase (NTB) and the splay-bend nematic phase (NSB), but their fine structure appears more complex than that considered so far. The presence of molecular chirality converts nonchiral NTP and NSB into new NTB phases. Surprisingly, the nonchiral NLP phase can stay stable even in the presence of intrinsic chirality.

  17. Subtle balance of ligand steric effects in Stille transmetalation.

    PubMed

    Ariafard, Alireza; Yates, Brian F

    2009-10-07

    Experimental results have previously suggested that the transmetalation step in the Stille reaction is hindered at one extreme by very bulky ligands L on the PdL(2) catalyst, yet at the other extreme, transmetalation is also found to be slow for small ligands. Our aim in this paper is to resolve this dilemma using computational chemistry and to show which ligand is best and why. With the use of density functional theory we show that the reason why L = P(t)Bu(3) retards transmetalation is because the bulky ligand hinders the coordination of the organostannane. On the other hand a small ligand such as L = PMe(3) leads to the formation of a very stable intermediate in the catalytic cycle which then requires a large activation energy for the transmetalation to proceed. The L = PPh(3) ligand appears to provide just the right balance in that it can readily coordinate the organostannane but avoids forming the very stable intermediate, and is thus the ligand of choice. L = PPh(2)Me is predicted to be the next best option, but L = PPhMe(2) is too small and forms an intermediate whose stability prevents further reaction in the transmetalation step. Our calculations are also able to account for the accelerating role of CsF in the transmetalation step of the Stille reaction. Finally, this work demonstrates the importance of taking into account the steric properties of the full ligand in theoretical studies of such reactions, rather than using small model phosphines.

  18. How Artists Overcome Creative Blocks.

    ERIC Educational Resources Information Center

    Hirst, Barbara

    1992-01-01

    Six practicing artists were interviewed about how they overcome creative blocks. Their responses indicated that feelings of self-doubt, fear, and depression accompany blocks but that relaxing and working on new directions and playing ideas off a supportive person helped to overcome such blocks. (DB)

  19. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Lynn Sparling; Bruce C. Buckheit; Daniel LoBue; and Richard P. Bowers

    2012-06-29

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  20. Mid-Atlantic Wind - Overcoming the Challenges

    SciTech Connect

    Daniel F. Ancona III; Kathryn E. George; Richard P. Bowers; Dr. Lynn Sparling; Bruce Buckheit; Daniel LoBue

    2012-05-31

    This study, supported by the US Department of Energy, Wind Powering America Program, Maryland Department of Natural Resources and Chesapeake Bay Foundation, analyzed barriers to wind energy development in the Mid-Atlantic region along with options for overcoming or mitigating them. The Mid-Atlantic States including Delaware, Maryland, North Carolina and Virginia, have excellent wind energy potential and growing demand for electricity, but only two utility-scale projects have been installed to date. Reasons for this apathetic development of wind resources were analyzed and quantified for four markets. Specific applications are: 1) Appalachian mountain ridgeline sites, 2) on coastal plains and peninsulas, 3) at shallow water sites in Delaware and Chesapeake Bays, Albemarle and Pamlico Sounds, and 4) at deeper water sites off the Atlantic coast. Each market has distinctly different opportunities and barriers. The primary barriers to wind development described in this report can be grouped into four categories; state policy and regulatory issues, wind resource technical uncertainty, economic viability, and public interest in environmental issues. The properties of these typologies are not mutually independent and do interact. The report concluded that there are no insurmountable barriers to land-based wind energy projects and they could be economically viable today. Likewise potential sites in sheltered shallow waters in regional bay and sounds have been largely overlooked but could be viable currently. Offshore ocean-based applications face higher costs and technical and wind resource uncertainties. The ongoing research and development program, revision of state incentive policies, additional wind measurement efforts, transmission system expansion, environmental baseline studies and outreach to private developers and stakeholders are needed to reduce barriers to wind energy development.

  1. Uncertainties in Steric Sea Level Change Estimation During the Satellite Altimeter Era: Concepts and Practices

    NASA Astrophysics Data System (ADS)

    MacIntosh, C. R.; Merchant, C. J.; von Schuckmann, K.

    2017-01-01

    This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However, tracking these steric changes still remains a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community "recipes" for quantifying the error covariances in observations and from sparse sampling and for estimating and propagating uncertainty across spatio-temporal scales.

  2. Uncertainties in Steric Sea Level Change Estimation During the Satellite Altimeter Era: Concepts and Practices

    NASA Astrophysics Data System (ADS)

    MacIntosh, C. R.; Merchant, C. J.; von Schuckmann, K.

    2016-10-01

    This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However, tracking these steric changes still remains a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community "recipes" for quantifying the error covariances in observations and from sparse sampling and for estimating and propagating uncertainty across spatio-temporal scales.

  3. Methyl rotational barriers in the E-forms of methyl esters

    NASA Astrophysics Data System (ADS)

    Wiberg, K. B.; Bohn, R. K.; Jimenez-Vazquez, H.

    1999-08-01

    Methyl nitrite has a normal 2.09 kcal/mol methyl rotation barrier in the Z-conformer, but only a small 0.03-0.06 kcal/mol barrier in the E-conformer as determined from microwave spectra (Turner et al., J. Phys. Chem., 83 (1979) 1473). Using dependable calculational methods, we show that this is a general result which carries over to another E-methyl ester, E-methyl formate, which does not have a sterically large substituent on the acid group, and is not specific to methyl nitrite alone. The small methyl barriers in E-methyl nitrite and E-methyl formate result from the absence of large steric interactions. Replacing H in the formyl group by sterically larger F, results in a normal O-methyl torsional barrier calculated to be 1.8 kcal/mol in the E-methyl fluoroformate.

  4. Overcoming Defensive Barriers to Communication: A Transactional Analysis Approach

    ERIC Educational Resources Information Center

    Carr-Smith, Norma

    1978-01-01

    Discusses executives' behaviors that create both defensive and supportive climates for workers, indicating ways in which transactional analysis can be used to interpret these behaviors and their effects. (RL)

  5. Improving The Perfect Storm: Overcoming Barriers To Climate Literacy

    NASA Astrophysics Data System (ADS)

    Tillinger, D.

    2015-12-01

    Students and scientists are trained to speak different languages. Climate science, and the geosciences more broadly, are strictly classroom topics, not subjects appropriate for casual conversation, social media, or creative projects. When students are aware of climate change through the mainstream media, it is nearly always in a political or technological context rather than a scientific one. However, given the opportunity, students are perfectly capable of not only understanding the science behind climate change, but communicating it to their peers. At the American Museum of Natural History, a group of underprivileged high school students visited Nature's Fury: The Science of Natural Disasters to learn about volcanoes, earthquakes, and climate change impacts. They were then able to write pitches and develop trailers for scientifically accurate, but still compelling, disaster movies. Arts in Parts, a creative outreach group formed as a response to Hurricane Sandy, facilitated a workshop in which younger children made mobiles from beach debris they collected while learning about the the threat of sea level rise locally and globally. Participants in an undergraduate natural disasters class wrote guides to understanding climate change that remained factual while showing great creativity and reflecting the personality of each student. Art, humor, and popular culture are the languages that society chooses to use; scientific literacy might benefit from their inclusion.

  6. Overcoming Barriers to Technology Adoption in Small Manufacturing Enterprises (SMEs)

    DTIC Science & Technology

    2003-06-01

    7 3.4 Adopting a Control-System-Modeling Tool.................................................8 3.5 Adapting Ecommerce and Manufacturing Execution...demonstration projects, workforce development, and technology development activities to document the benefits of these technologies and the steps needed to...SMEs to support defense manufacturers by demonstrating the benefits of implementing commercially available software and information technologies

  7. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial…

  8. Public opinion and organ donation suggestions for overcoming barriers.

    PubMed

    Cantarovich, Félix

    2005-01-01

    Getting organs for transplantation depends on people's decision; thus, public opinion is essential to finding a solution to this problem. Efforts to improve organ shortage focus on: 1) Living, unrelated donation, 2) increasing marginal donors and 3) proposing economic support for donors. Paradoxically, no initiative has been suggested to modify public opinion towards cadaver donors. Several reasons explain the resistance to donating cadaver organs: Lack of awareness, religious uncertainties, distrust of medicine, hostility to new ideas, and misinformation. Education should be used to reshape public opinion about the use of organs for transplantation. Society should accept that "using" body parts is moral and offers a source of health for everybody. The concept that using cadaver organs implies sharing a source of health might be a social agreement between all members of Society. Suggestions for improving organ shortage include: 1) Society should understand that during one's life one may be just as easily a potential organ receiver as one is an organ donor. 2) Cadaver organs are an irreplaceable source of health. 3) As self-interest is one obstacle to donating cadaver organs, the "concept that allowing the use of our organs after death represents a chance of sharing health for everybody" may be useful for a change of attitude. Even though a poll among transplant professionals supported this suggestion, an international public survey should be carried out to evaluate people's reaction to this message.

  9. Overcoming Barriers to Educational Restructuring: A Call for System Literacy.

    ERIC Educational Resources Information Center

    McGonagill, Grady

    The drive for systemic reform in education reflects a widespread hunger in all sectors of society to make sense of the whole, as is shown in the increasing recognition of people in organizations of the interrelatedness of the organizations' parts. However, many attempts at systemic reform are hampered by the lack of a common view of what an…

  10. Wind Power in Australia: Overcoming Technological and Institutional Barriers

    ERIC Educational Resources Information Center

    Healey, Gerard; Bunting, Andrea

    2008-01-01

    Until recently, Australia had little installed wind capacity, although there had been many investigations into its potential during the preceding decades. Formerly, state-owned monopoly utilities showed only token interest in wind power and could dictate the terms of energy debates. This situation changed in the late 1990s: Installed wind capacity…

  11. Overcoming language barriers for non-English speaking patients.

    PubMed

    Duffy, M M; Alexander, A

    1999-10-01

    Although some of the resources or services listed may seem expensive, it is cheaper to use these than to face a malpractice suit for failure to provide patients with limited English access to services equal to those provided to English speakers. The University of California at San Francisco (UCSF), one of the top three ranking research hospitals in the U.S., had a suit filed against it by the American Civil Liberties Union (ACLU) claiming failure to provide adequate translation services for the patient population. The university is now a participant in a statewide effort to provide access to well-trained translator services to the patient population. This effort and the development of an in-house interpreter services department has contributed to a competitive edge for UCSF in the area of patient services and satisfaction as well as attracting more Medicaid patients, which increases their revenues.

  12. Postsecondary Correctional Education: Recognizing and Overcoming Barriers to Success

    ERIC Educational Resources Information Center

    Palmer, Shelby M.

    2012-01-01

    Postsecondary programs offering vocational training and college credit to eligible inmates have had difficulty finding a place in the U.S. correctional system. Politically motivated restrictions preventing inmates from receiving federal funds for college resulted in drastic program closures. Although new laws restored funding to select inmates,…

  13. Overcoming Barriers to Technology Use in Teacher Preparation Programs

    ERIC Educational Resources Information Center

    Brzycki, Dolores; Dudt, Kurt

    2005-01-01

    Indiana, Clarion, and Edinboro Universities of Pennsylvania are completing a PT3 grant, funded by the U.S. Department of Education, entitled "Preparing Teachers for the Digital Age." The grant made great progress in infusing technology into the teacher preparation curriculum possible, and participating faculty know how far they have…

  14. Wind Power in Australia: Overcoming Technological and Institutional Barriers

    ERIC Educational Resources Information Center

    Healey, Gerard; Bunting, Andrea

    2008-01-01

    Until recently, Australia had little installed wind capacity, although there had been many investigations into its potential during the preceding decades. Formerly, state-owned monopoly utilities showed only token interest in wind power and could dictate the terms of energy debates. This situation changed in the late 1990s: Installed wind capacity…

  15. Overcoming Barriers to Technology Use in Teacher Preparation Programs

    ERIC Educational Resources Information Center

    Brzycki, Dolores; Dudt, Kurt

    2005-01-01

    Indiana, Clarion, and Edinboro Universities of Pennsylvania are completing a PT3 grant, funded by the U.S. Department of Education, entitled "Preparing Teachers for the Digital Age." The grant made great progress in infusing technology into the teacher preparation curriculum possible, and participating faculty know how far they have…

  16. Overcoming the barriers to diagnosis of Morquio A syndrome.

    PubMed

    Bhattacharya, Kaustuv; Balasubramaniam, Shanti; Choy, Yew Sing; Fietz, Michael; Fu, Antony; Jin, Dong Kyu; Kim, Ok-Hwa; Kosuga, Motomichi; Kwun, Young Hee; Inwood, Anita; Lin, Hsiang-Yu; McGill, Jim; Mendelsohn, Nancy J; Okuyama, Torayuki; Samion, Hasri; Tan, Adeline; Tanaka, Akemi; Thamkunanon, Verasak; Toh, Teck-Hock; Yang, Albert D; Lin, Shuan-Pei

    2014-11-30

    Morquio A syndrome is an autosomal recessive lysosomal storage disease often resulting in life-threatening complications. Early recognition and proficient diagnosis is imperative to facilitate prompt treatment and prevention of clinical complications. Experts in Asia Pacific reviewed medical records focusing on presenting signs and symptoms leading to a diagnosis of Morquio A syndrome. Eighteen patients (77% female) had a mean (median; min, max) age of 77.1 (42.0; 0.0, 540.0) months at symptom onset, 78.9 (42.0; 4.5, 540.0) months at presentation and 113.8 (60.0; 7.0, 540.0) months at diagnosis. Orthopedic surgeons and pediatricians were most frequently consulted pre-diagnosis while clinical geneticists/metabolic specialists most frequently made the diagnosis. Delayed diagnoses were due to atypical symptoms for 5 patients (28%), while 4 patients (22%) experienced each of subtle symptoms, symptoms commonly associated with other diseases, or false-negative urine glycosaminoglycan analysis. Two patients (11%) each experienced overgrowth within the first year of life. Two patients with Morquio A syndrome (11%) were diagnosed with craniosynostosis and 1 (6%) for each of Legg-Calvé-Perthes disease, Leri-Weill syndrome, and pseudoachondroplasia. Early radiographic features of Morquio A syndrome led to more efficient diagnosis. Increased awareness of clinical symptomology overlapping with Morquio A syndrome is essential. Clinicians encountering patients with certain skeletal dysplasia should consider Morquio A syndrome in their differential diagnosis. Atypical or subtle symptoms should not eliminate Morquio A syndrome from the differential diagnosis, especially for patients who may have non-classical phenotype of Morquio A syndrome.

  17. Overcoming Barriers to Writing: Computer Support for Basic Writing Skills.

    ERIC Educational Resources Information Center

    MacArthur, Charles A.

    1999-01-01

    Reviews specific ways in which computers can support the basic transcription processes involved in writing, focusing on computer applications that go beyond word processing, including spelling and grammar checkers, speech synthesis, word prediction, and speech recognition. Focuses only on writing mechanics, and clarifies the extent to which…

  18. Bicycle helmets: overcoming barriers to use and increasing effectiveness.

    PubMed

    Rezendes, Jennifer L

    2006-02-01

    Bicycle riding is a popular recreational activity among children, yet it is not without potential severe consequences such as traumatic brain injury and death. Despite available information attesting to the benefits of the use of bicycle safety helmets, many children still do not wear them. There are several promoting and discouraging factors that influence wearing bicycle helmets. The purposes of this article are to (1) explore current research and discuss these promoting and obstructing factors to child bicycle helmet use and to (2) provide recommendations for improving the compliance of bicycle helmet use among children. Results of the literature review have significant implications for improving the safety of children.

  19. Using mobile technology to overcome language barriers in medicine

    PubMed Central

    Thyer, IA; Hayne, D; Katz, DJ

    2014-01-01

    Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices. PMID:25198966

  20. Overcoming Barriers to Total Quality Management in Colleges and Universities.

    ERIC Educational Resources Information Center

    Winter, Robert S.

    1991-01-01

    To implement Total Quality Management concepts successfully, colleges and universities must change their cultures significantly. In higher education, with its organizational characteristics and traditions, authority relationships between faculty and administrators must be recognized, and some changes in the role and attention of leaders must…

  1. Autophagy core machinery: overcoming spatial barriers in neurons.

    PubMed

    Ariosa, Aileen R; Klionsky, Daniel J

    2016-11-01

    Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One type of autophagy, macroautophagy, is a tightly regulated process facilitated by autophagy-related (Atg) proteins that must communicate effectively and act in concert to enable the de novo formation of the phagophore, its maturation into an autophagosome, and its subsequent targeting and fusion with the lysosome or the vacuole. Autophagy plays a significant role in physiology, and its dysregulation has been linked to several diseases, which include certain cancers, cardiomyopathies, and neurodegenerative diseases. Here, we summarize the key processes and the proteins that make up the macroautophagy machinery. We also briefly highlight recently uncovered molecular mechanisms specific to neurons allowing them to uniquely regulate this catabolic process to accommodate their complicated architecture and non-dividing state. Overall, these distinct mechanisms establish a conceptual framework addressing how macroautophagic dysfunction could result in maladies of the nervous system, providing possible therapeutic avenues to explore with a goal of preventing or curing such diseases.

  2. What Changes Education? An Action Research to Overcome Barriers

    ERIC Educational Resources Information Center

    Eskicioglu, Yeser Eroglu

    2016-01-01

    According to the National Disabled People Data Base within Ministry of Family and Social Policies (Özveri), there are 1.559.222 disabled people in Turkey. If this rate would be linked to the families of the disabled people, the number of people who spend time with disabled individuals would increase to 10 million. This number corresponds to 12.5%…

  3. Overcoming Barriers to Workers' Education. Topic Paper No. 2.

    ERIC Educational Resources Information Center

    Schaefer, Dennis P.

    This booklet is intended to assist union representatives at plants in counseling workers who want to pursue college studies. Presented first is a hypothetical case study of a 37-year-old printer who would like to attend college at night but who is beset with time, family, and money problems. The remainder of the booklet consists of guidelines and…

  4. Postsecondary Correctional Education: Recognizing and Overcoming Barriers to Success

    ERIC Educational Resources Information Center

    Palmer, Shelby M.

    2012-01-01

    Postsecondary programs offering vocational training and college credit to eligible inmates have had difficulty finding a place in the U.S. correctional system. Politically motivated restrictions preventing inmates from receiving federal funds for college resulted in drastic program closures. Although new laws restored funding to select inmates,…

  5. Using mobile technology to overcome language barriers in medicine.

    PubMed

    Chang, D T S; Thyer, I A; Hayne, D; Katz, D J

    2014-09-01

    Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices.

  6. Overcoming Barriers: Engaging Younger Students in an Online Intercultural Exchange

    ERIC Educational Resources Information Center

    Peiser, Gillian

    2015-01-01

    This paper reports on a small-scale project involving an online school exchange between two classes of 12-/13-year olds located in the North of England and the Ruhr area of Germany. The overarching aim of the project was to develop intercultural understanding in foreign language learning through communication in an online environment. Analysing…

  7. Overcoming the Financial Aid Barrier for E-Learners

    ERIC Educational Resources Information Center

    Chaloux, Bruce

    2008-01-01

    Financial aid systems help make higher education available to all who can benefit. To "adjust" the existing financial aid system to make it more student friendly and open doors currently closed to many part-time learners and students with the greatest financial challenges, state policy changes and greater private sector initiatives…

  8. Overcoming barriers to residential conservation: do energy audits help

    SciTech Connect

    Hoffman, W.L.

    1982-12-01

    A study on the effects of energy audits on the pace and choice of household investment in energy-saving improvements in the home is reported. An evaluation based on the household's assessment of the usefulness of the audit which was provided for their home was performed. The number and types of recent conservation actions among audited and unaudited samples of households are compared. The audit's effect on household knowledge about the economically attractive options for their home and on the choice of recent improvements is assessed. Possible reasons are suggested for the weak effect of audits in stimulating activity and reorienting investment choices. (LEW)

  9. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    NASA Astrophysics Data System (ADS)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  10. Overcoming Barriers for "Niche" Learners Through Distance Education.

    ERIC Educational Resources Information Center

    Miller, Lawrence G.; Hyatt, Sue Y.; Brennan, Joyce; Bertani, Raymond; Trevor, Thomas

    1999-01-01

    Focuses on students who fit into "niches," and discusses how the Chattanooga State Technical Community College's distance-learning program accommodates these learners. Describes five "niche" learner categories: students with disabilities, power-line maintenance technicians, emergency-service personnel, truckers, and industrial…

  11. Overcoming barriers to priority setting using interdisciplinary methods.

    PubMed

    Peacock, Stuart; Mitton, Craig; Bate, Angela; McCoy, Bonnie; Donaldson, Cam

    2009-10-01

    Ten years ago, Holm's highly influential paper "Goodbye to the simple solutions: the second phase of priority setting" was published [Holm S. Goodbye to the simple solutions: the second phase of priority setting in health care. British Medical Journal 1998;317:1000-7]. Whilst attending the 2nd International Conference on Priorities in Health Care in London, Holm argued that the search for a rational set of decision-making rules was no longer adequate. Instead, the priority setting process itself was now thought to be more complex. Ten years later, the Conference returns to the UK for the first time, and it is timely to describe some new tools intended to assist both researchers and decision-makers seeking to develop both rational and fair and legitimate priority setting processes. In this paper we argue that to do so, researchers and decision-makers need to adopt an interdisciplinary and collaborative approach to priority setting. We focus on program budgeting and marginal analysis (PBMA) and bring together three hitherto separate interdisciplinary strands of the PBMA literature. Our aim is to assist researchers and decision-makers seeking to effectively develop and implement PBMA in practice. Specifically, we focus on the use of multi-criteria decision analysis, participatory action research, and accountability for reasonableness, drawn from the disciplines of decision analysis, sociology, and ethics respectively.

  12. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases

    PubMed Central

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs’ unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a “water-soluble” amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug’s therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  13. Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

    DOE PAGES

    Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.; ...

    2016-09-08

    The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. Lastly, this approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

  14. Use of steric encumbrance to develop conjugated nanoporous polymers for metal-free catalytic hydrogenation

    SciTech Connect

    Tian, Chengcheng; Zhu, Xiang; Abney, Carter W.; Tian, Ziqi; Jiang, De-en; Han, Kee Sung; Mahurin, Shannon M.; Washton, Nancy M.; Dai, Sheng

    2016-01-01

    The design and synthesis of metal-free heterogeneous catalysts for efficient hydrogenation remains a great challenge. Here we report a novel approach to create conjugated nanoporous polymers with efficient hydrogenation activities toward unsaturated ketones by leveraging the innate steric encumbrance. The steric bulk of the framework as well as the local sterics of the Lewis basic sites within the polymeric skeleton result in the generation of the putative catalyst. This approach opens up new possibilities for the development of innovative metal-free heterogeneous catalysts.

  15. Perspective: Vibrational-induced steric effects in bimolecular reactions

    NASA Astrophysics Data System (ADS)

    Liu, Kopin

    2015-02-01

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C-H stretch-excited CHD3(v1 = 1) with F, Cl, and O(3P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O(3P) + CHD3(v1 = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical "negative" lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD3. On the contrary, the interaction between O(3P) and CHD3(v1 = 1) behaves as a "positive" lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD3(v1 = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi's rules, are made.

  16. Perspective: Vibrational-induced steric effects in bimolecular reactions

    SciTech Connect

    Liu, Kopin

    2015-02-28

    The concept of preferred collision geometry in a bimolecular reaction is at the heart of reaction dynamics. Exemplified by a series of crossed molecular beam studies on the reactions of a C–H stretch-excited CHD{sub 3}(v{sub 1} = 1) with F, Cl, and O({sup 3}P) atoms, two types of steric control of chemical reactivity will be highlighted. A passive control is governed in a reaction with strong anisotropic entry valley that can significantly steer the incoming trajectories. This disorientation effect is illustrated by the F and O({sup 3}P) + CHD{sub 3}(v{sub 1} = 1) reactions. In the former case, the long-range anisotropic interaction acts like an optical “negative” lens by deflecting the trajectories away from the favored transition-state geometry, and thus inhibiting the bond rupture of the stretch-excited CHD{sub 3}. On the contrary, the interaction between O({sup 3}P) and CHD{sub 3}(v{sub 1} = 1) behaves as a “positive” lens by funneling the large impact-parameter collisions into the cone of acceptance, and thereby enhances the reactivity. As for reactions with relatively weak anisotropic interactions in the entry valley, an active control can be performed by exploiting the polarization property of the infrared excitation laser to polarize the reactants in space, as demonstrated in the reaction of Cl with a pre-aligned CHD{sub 3}(v{sub 1} = 1) reactant. A simpler case, the end-on versus side-on collisions, will be elucidated for demonstrating a means to disentangle the impact-parameter averaging. A few general remarks about some closely related issues, such as mode-, bond-selectivity, and Polanyi’s rules, are made.

  17. Electronic and Steric Effects in Binding of Deep Cavitands

    PubMed Central

    Hooley, Richard J.; Shenoy, Siddhartha R.; Rebek, Julius

    2009-01-01

    A deep, self-folding cavitand responds to minor electronic differences between suitably sized adamantane guests. Binding constants range from <0.5 to 4000 M-1 for guests as similar as 1-bromoadamantane and 1-cyanoadamantane. The barriers to guest exchange also vary up to 3 kcal mol-1. PMID:18989966

  18. Cyclic (Alkyl)(Amino)Carbene Complexes of Rhodium and Nickel and Their Steric and Electronic Parameters.

    PubMed

    Paul, Ursula S D; Sieck, Carolin; Haehnel, Martin; Hammond, Kai; Marder, Todd B; Radius, Udo

    2016-07-25

    N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAAC(methyl) , which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands.

  19. Comprehensive Examination of Barriers to Employment among Persons Who Are Blind or Visually Impaired.

    ERIC Educational Resources Information Center

    Crudden, Adele; McBroom, Lynn W.; Skinner, Amy L.; Moore, J. Elton

    A survey of 166 employed persons with visual impairments investigated major barriers to employment, how these barriers were overcome, and their perceptions on why they were successful in overcoming barriers when many individuals are not successful. Results of the survey indicate that the primary barriers to employment were employer attitudes,…

  20. Viscoelastic properties of sterically stabilised emulsions and their stability.

    PubMed

    Tadros, Tharwat

    2015-08-01

    The interaction forces between emulsion droplets containing adsorbed polymeric surfactants and the theory of steric stabilisation are briefly described. The results for the viscoelastic properties of O/W emulsions that are stabilised with partially hydrolysed poly(vinyl acetate) that is commonly referred to as poly(vinyl alcohol) (PVA) with 4% vinyl acetate are given. The effect of the oil volume fraction, addition of electrolytes and increasing temperature is described. This allows one to obtain various parameters such as the adsorbed layer thickness, the critical flocculation concentration of electrolyte (CFC) and critical flocculation temperature (CFT) at constant electrolyte concentration. The viscoelastic properties of O/W emulsions stabilised with an A-B-A block copolymer of polyethylene oxide (A) and polypropylene oxide (B) are described. These emulsions behave as viscoelastic liquids showing a cross-over-point between G' (the elastic component of the complex modulus) and G″ (the viscous component of the complex modulus) at a characteristic frequency. Plots of G' and G″ versus oil volume fraction ϕ show the transition from predominantly viscous to predominantly elastic response at a critical volume fraction ϕ(c). The latter can be used to estimate the adsorbed layer thickness of the polymeric surfactants. Results are also shown for W/O emulsions stabilised with an A-B-A block copolymer of polyhydroxystearic acid (PHS, A) and polyethylene oxide (PEO, B). The viscosity volume fraction curves could be fitted to the Dougherty-Krieger equation for hard-spheres. The results could be applied to give an estimate of the adsorbed layer thickness Δ which shows a decrease with increase of the water volume fraction. This is due to the interpenetration and/or compression of the PHS layers on close approach of the water droplets on increasing the water volume fraction. The last section of the review gives an example of O/W emulsion stability using an AB(n) graft

  1. Integral steric asymmetry in the inelastic scattering of NO(X(2)Π).

    PubMed

    Brouard, M; Gordon, S D S; Hackett Boyle, A; Heid, C G; Nichols, B; Walpole, V; Aoiz, F J; Stolte, S

    2017-01-07

    The integral steric asymmetry for the inelastic scattering of NO(X) by a variety of collision partners was recorded using a crossed molecular beam apparatus. The initial state of the NO(X, v = 0, j = 1/2, Ω=1/2, ϵ=-1,f) molecule was selected using a hexapole electric field, before the NO bond axis was oriented in a static electric field, allowing probing of the scattering of the collision partner at either the N- or O-end of the molecule. Scattered NO molecules were state selectively probed using (1 + 1') resonantly enhanced multiphoton ionisation, coupled with velocity-map ion imaging. Experimental integral steric asymmetries are presented for NO(X) + Ar, for both spin-orbit manifolds, and Kr, for the spin-orbit conserving manifold. The integral steric asymmetry for spin-orbit conserving and changing transitions of the NO(X) + O2 system is also presented. Close-coupled quantum mechanical scattering calculations employing well-tested ab initio potential energy surfaces were able to reproduce the steric asymmetry observed for the NO-rare gas systems. Quantum mechanical scattering and quasi-classical trajectory calculations were further used to help interpret the integral steric asymmetry for NO + O2. Whilst the main features of the integral steric asymmetry of NO with the rare gases are also observed for the O2 collision partner, some subtle differences provide insight into the form of the underlying potentials for the more complex system.

  2. Integral steric asymmetry in the inelastic scattering of NO(X2Π)

    NASA Astrophysics Data System (ADS)

    Brouard, M.; Gordon, S. D. S.; Hackett Boyle, A.; Heid, C. G.; Nichols, B.; Walpole, V.; Aoiz, F. J.; Stolte, S.

    2017-01-01

    The integral steric asymmetry for the inelastic scattering of NO(X) by a variety of collision partners was recorded using a crossed molecular beam apparatus. The initial state of the NO(X, v = 0, j = 1/2, Ω =1 /2 , ɛ =-1 ,f ) molecule was selected using a hexapole electric field, before the NO bond axis was oriented in a static electric field, allowing probing of the scattering of the collision partner at either the N- or O-end of the molecule. Scattered NO molecules were state selectively probed using (1 + 1') resonantly enhanced multiphoton ionisation, coupled with velocity-map ion imaging. Experimental integral steric asymmetries are presented for NO(X) + Ar, for both spin-orbit manifolds, and Kr, for the spin-orbit conserving manifold. The integral steric asymmetry for spin-orbit conserving and changing transitions of the NO(X) + O2 system is also presented. Close-coupled quantum mechanical scattering calculations employing well-tested ab initio potential energy surfaces were able to reproduce the steric asymmetry observed for the NO-rare gas systems. Quantum mechanical scattering and quasi-classical trajectory calculations were further used to help interpret the integral steric asymmetry for NO + O2. Whilst the main features of the integral steric asymmetry of NO with the rare gases are also observed for the O2 collision partner, some subtle differences provide insight into the form of the underlying potentials for the more complex system.

  3. Quantifying the role of steric constraints in nucleosome positioning.

    PubMed

    Rube, H Tomas; Song, Jun S

    2014-02-01

    Statistical positioning, the localization of nucleosomes packed against a fixed barrier, is conjectured to explain the array of well-positioned nucleosomes at the 5' end of genes, but the extent and precise implications of statistical positioning in vivo are unclear. We examine this hypothesis quantitatively and generalize the idea to include moving barriers as well as nucleosomes actively packed against a barrier. Early experiments noted a similarity between the nucleosome profile aligned and averaged across genes and that predicted by statistical positioning; however, we demonstrate that aligning random nucleosomes also generates the same profile, calling the previous interpretation into question. New rigorous results reformulate statistical positioning as predictions on the variance structure of nucleosome locations in individual genes. In particular, a quantity termed the variance gradient, describing the change in variance between adjacent nucleosomes, is tested against recent high-throughput nucleosome sequencing data. Constant variance gradients provide support for generalized statistical positioning in ∼ 50% of long genes. Genes that deviate from predictions have high nucleosome turnover and cell-to-cell gene expression variability. The observed variance gradient suggests an effective nucleosome size of 158 bp, instead of the commonly perceived 147 bp. Our analyses thus clarify the role of statistical positioning in vivo.

  4. Evaluation of donor and steric properties of anionic ligands on high valent transition metals.

    PubMed

    DiFranco, Stephen A; Maciulis, Nicholas A; Staples, Richard J; Batrice, Rami J; Odom, Aaron L

    2012-01-16

    Synthetic protocols and characterization data for a variety of chromium(VI) nitrido compounds of the general formula NCr(NPr(i)(2))(2)X are reported, where X = NPr(i)(2) (1), I (2), Cl (3), Br (4), OTf (5), 1-adamantoxide (6), OSiPh(3) (7), O(2)CPh (8), OBu(t)(F6) (9), OPh (10), O-p-(OMe)C(6)H(4) (11), O-p-(SMe)C(6)H(4) (12), O-p-(Bu(t))C(6)H(4) (13), O-p-(F)C(6)H(4) (14), O-p-(Cl)C(6)H(4) (15), O-p-(CF(3))C(6)H(4) (16), OC(6)F(5) (17), κ(O)-N-oxy-phthalimide (18), SPh (19), OCH(2)Ph (20), NO(3) (21), pyrrolyl (22), 3-C(6)F(5)-pyrrolyl (23), 3-[3,5-(CF(3))(2)C(6)H(3)]pyrrolyl (24), indolyl (25), carbazolyl (26), N(Me)Ph (27), κ(N)-NCO (28), κ(N)-NCS (29), CN (30), NMe(2) (31), F (33). Several different techniques were employed in the syntheses, including nitrogen-atom transfer for the formation of 1. A cationic chromium complex [NCr(NPr(i)(2))(2)(DMAP)]BF(4) (32) was used as an intermediate for the production of 33, which was produced by tin-catalyzed degredation of the salt. Using spin saturation transfer or line shape analysis, the free energy barriers for diisopropylamido rotation were studied. It is proposed that the estimated enthalpic barriers, Ligand Donor Parameters (LDPs), for amido rotation can be used to parametrize the donor abilities of this diverse set of anionic ligands toward transition metal centers in low d-electron counts. The new LDPs do not correlate well to the pK(a) value of X. Conversely, the LDP values of phenoxide ligands do correlate with Hammett parameters for the para-substituents. Literature data for (13)C NMR chemical shifts for a tungsten-based system with various X ligands plotted versus LDP provided a linear fit. In addition, the angular overlap model derived e(σ) + e(π) values for chromium(III) ammine complexes correlate with LDP values. Also discussed is the correlation with XTiCp*(2) spectroscopic data. X-ray diffraction has been used used to characterize 31 of the compounds. From the X-ray diffraction data, steric

  5. Boron and aluminum complexes of sterically demanding phosphinimines and phosphinimides.

    PubMed

    Courtenay, Silke; Walsh, Denise; Hawkeswood, Sarah; Wei, Pingrong; Das, Anjan Kumar; Stephan, Douglas W

    2007-04-30

    Reactions of sterically demanding phosphinimines R3PNH [R=i-Pr (1), t-Bu (2)] were examined. Reactions with B(C6F5)3 formed the adducts (R3PNH)B(C6F5)3 [R=i-Pr (3), t-Bu (4)] in high yield. On the other hand, 2 reacts with HB(OBu)2, evolving H2 to give t-Bu3PNB(OBu)2 (5). The reaction of 2 equiv of 2 with BH3.SMe2 affords the species (t-Bu3PN)2BH (6). In contrast, the reaction of n-Bu(t-Bu)2PNH with BH3.SMe2 results in the formation of the robust adduct n-Bu(t-Bu)2PNH.BH3 (8). An alternative route to borane-phosphinimide complexes involves Me3SiCl elimination, as exemplified by the reaction of BCl2Ph with n-Bu3PNSiMe3, which gives the product n-Bu3PNBCl(Ph) (9). The corresponding reactions of the parent phosphinimines 1 and 2 with AlH3.NMe2Et give the dimers [(mu-i-Pr3PN)AlH2]2 (10) and [(mu-t-Bu3PN)AlH2]2 (11). Species 11 reacts further with Me3SiO3SCF3 to provide [(mu-t-Bu3PN)AlH(OSO2CF3)]2 (12). The reaction of the lithium salt [t-Bu3PNLi]4 (13) with BCl3 proceeds smoothly to give t-Bu3PNBCl2 (14), which is readily alkylated to give t-Bu3PNBMe2 (15). Subsequent reaction of 15 with B(C6F5)3 results in methyl abstraction and the formation of [(mu-t-Bu3PN)BMe]2[MeB(C6F5)3]2 (16). The reaction of 13 in a 2:1 ratio with BCl3 gives the salt [(t-Bu3PN)2B]Cl (17). This species can be methylated to give (t-Bu3PN)2BMe (18), which undergoes subsequent reaction with [Ph3C][X] (X=[B(C6F5)4], [PF6]) to form the related salts [(t-Bu3PN)2B][B(C6F5)4] (19) and [(t-Bu3PN)2B][PF6] (20), respectively. Analogous reactions with [Ph3C][BF4] afforded [t-Bu3PNBF2]2 (21). Compounds 3, 4, 6, 8, 11, 12, 17, 19, and 21 were characterized by X-ray crystallography.

  6. Overcoming Exclusion through Adult Learning.

    ERIC Educational Resources Information Center

    Nash, Ian; Walshe, John

    Strategies for overcoming exclusion through adult learning were identified through case studies of 19 initiatives in the following countries: Belgium; Mexico; the Netherlands; Norway; Portugal; and the United Kingdom. The study programs involved a diverse array of formal, nonformal, and informal public sector, community, and enterprise-based…

  7. Steric gate variants of UmuC confer UV hypersensitivity on Escherichia coli.

    PubMed

    Shurtleff, Brenna W; Ollivierre, Jaylene N; Tehrani, Mohammad; Walker, Graham C; Beuning, Penny J

    2009-08-01

    Y family DNA polymerases are specialized for replication of damaged DNA and represent a major contribution to cellular resistance to DNA lesions. Although the Y family polymerase active sites have fewer contacts with their DNA substrates than replicative DNA polymerases, Y family polymerases appear to exhibit specificity for certain lesions. Thus, mutation of the steric gate residue of Escherichia coli DinB resulted in the specific loss of lesion bypass activity. We constructed variants of E. coli UmuC with mutations of the steric gate residue Y11 and of residue F10 and determined that strains harboring these variants are hypersensitive to UV light. Moreover, these UmuC variants are dominant negative with respect to sensitivity to UV light. The UV hypersensitivity and the dominant negative phenotype are partially suppressed by additional mutations in the known motifs in UmuC responsible for binding to the beta processivity clamp, suggesting that the UmuC steric gate variant exerts its effects via access to the replication fork. Strains expressing the UmuC Y11A variant also exhibit decreased UV mutagenesis. Strikingly, disruption of the dnaQ gene encoding the replicative DNA polymerase proofreading subunit suppressed the dominant negative phenotype of a UmuC steric gate variant. This could be due to a recruitment function of the proofreading subunit or involvement of the proofreading subunit in a futile cycle of base insertion/excision with the UmuC steric gate variant.

  8. Diffusion barriers

    NASA Technical Reports Server (NTRS)

    Nicolet, M. A.

    1983-01-01

    The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

  9. Carbamate stabilities of sterically hindered amines from quantum chemical methods: relevance for CO2 capture.

    PubMed

    Gangarapu, Satesh; Marcelis, Antonius T M; Zuilhof, Han

    2013-12-02

    The influence of electronic and steric effects on the stabilities of carbamates formed from the reaction of CO2 with a wide range of alkanolamines was investigated by quantum chemical methods. For the calculations, B3LYP, M11-L, MP2, and spin-component-scaled MP2 (SCS-MP2) methods were used, coupled with SMD and SM8 solvation models. A reduction in carbamate stability leads to an increased CO2 absorption capacity of the amine and a reduction of the energy required for solvent regeneration. Important factors for the reduction of the carbamate stability were an increase in steric hindrance around the nitrogen atom, charge on the N atom and intramolecular hydrogen bond strength. The present study indicates that secondary ethanolamines with sterically hindering groups near the N atom show significant potential as candidates for industrial CO2-capture solvents.

  10. Multiple solutions of steady-state Poisson-Nernst-Planck equations with steric effects

    NASA Astrophysics Data System (ADS)

    Lin, Tai-Chia; Eisenberg, Bob

    2015-07-01

    Experiments measuring currents through single protein channels show unstable currents. Channels switch between ‘open’ or ‘closed’ states in a spontaneous stochastic process called gating. Currents are either (nearly) zero or at a definite level, characteristic of each type of protein, independent of time, once the channel is open. The steady state Poisson-Nernst-Planck equations with steric effects (PNP-steric equations) describe steady current through the open channel quite well, in a wide variety of conditions. Here we study the existence of multiple solutions of steady state PNP-steric equations to see if they themselves, without modification or augmentation, can describe two levels of current. We prove that there are two steady state solutions of PNP-steric equations for (a) three types of ion species (two types of cations and one type of anion) with a positive constant permanent charge, and (b) four types of ion species (two types of cations and their counter-ions) with a constant permanent charge but no sign condition. The excess currents (due to steric effects) associated with these two steady state solutions are derived and expressed as two distinct formulas. Our results indicate that PNP-steric equations may become a useful model to study spontaneous gating of ion channels. Spontaneous gating is thought to involve small structural changes in the channel protein that perhaps produce large changes in the profiles of free energy that determine ion flow. Gating is known to be modulated by external structures. Both can be included in future extensions of our present analysis.

  11. Barriers to exotic weed management

    Treesearch

    Faith T. Campbell

    1998-01-01

    In order to increase effective efforts to reduce the impacts of invasive alien plant species· on our natural areas, we must overcome numerous barriers. Some of these are technical in nature, e.g., determining the most appropriate control method for a specific species in a particular ecosystem, or devising a better program to exclude new invasive plant species from our...

  12. Overcoming Stereotypes, Discovering Hidden Capitals

    ERIC Educational Resources Information Center

    Beckett, Lori; Wrigley, Terry

    2014-01-01

    This article presents a model of teacher research supported by academic partners to develop a better understanding of the barriers to education faced by young people growing up in poverty. It critiques politicians' demands for teachers to "close the gap" for ignoring the cumulative intergenerational effects of deprivation. The authors…

  13. Overcoming Stereotypes, Discovering Hidden Capitals

    ERIC Educational Resources Information Center

    Beckett, Lori; Wrigley, Terry

    2014-01-01

    This article presents a model of teacher research supported by academic partners to develop a better understanding of the barriers to education faced by young people growing up in poverty. It critiques politicians' demands for teachers to "close the gap" for ignoring the cumulative intergenerational effects of deprivation. The authors…

  14. Epistemological barriers to radical behaviorism.

    PubMed

    O'Donohue, W T; Callaghan, G M; Ruckstuhl, L E

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers.

  15. Epistemological barriers to radical behaviorism

    PubMed Central

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  16. New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.

    PubMed Central

    Beugin, S; Edwards, K; Karlsson, G; Ollivon, M; Lesieur, S

    1998-01-01

    Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C16G2) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C16G2/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks. PMID:9635773

  17. Implications of sterically constrained n-butane oxidation reactions on the reaction mechanism and selectivity to 1-butanol

    NASA Astrophysics Data System (ADS)

    Dix, Sean T.; Gómez-Gualdrón, Diego A.; Getman, Rachel B.

    2016-11-01

    Density functional theory (DFT) is used to analyze the reaction network in n-butane oxidation to 1-butanol over a Ag/Pd alloy catalyst under steric constraints, and the implications on the ability to produce 1-butanol selectively using MOF-encapsulated catalysts are discussed. MOFs are porous crystalline solids comprised of metal nodes linked by organic molecules. Recently, they have been successfully grown around metal nanoparticle catalysts. The resulting porous networks have been shown to promote regioselective chemistry, i.e., hydrogenation of trans-1,3-hexadiene to 3-hexene, presumably by forcing the linear alkene to stand "upright" on the catalyst surface and allowing only the terminal C-H bonds to be activated. In this work, we extend this concept to alkane oxidation. Our goal is to determine if a MOF-encapsulated catalyst could be used to selectively produce 1-butanol. Reaction energies and activation barriers are presented for more than 40 reactions in the pathway for n-butane oxidation. We find that C-H bond activation proceeds through an oxygen-assisted pathway and that butanal and 1-butanol are some of the possible products.

  18. Steric and energetic properties of the Cl- C6H6 Arn heterocluster

    NASA Astrophysics Data System (ADS)

    Albertí, M.; Castro, A.; Laganà, A.; Moix, M.; Pirani, F.; Cappelletti, D.

    2006-04-01

    The dynamics of heteroclusters containing argon, benzene and chlorine has been investigated using a recently proposed potential energy functional that takes into account both the electrostatic and the non-electrostatic contributions to the overall noncovalent interaction. Related steric and energetic properties are compared with those homologous cationic clusters.

  19. Steric and mass-induced sea level variations in the Mediterranean Sea revisited

    NASA Astrophysics Data System (ADS)

    GarcíA-GarcíA, D.; Chao, B. F.; Boy, J.-P.

    2010-12-01

    The total sea level variation (SLV) is the combination of steric and mass-induced SLV, whose exact shares are key to understanding the oceanic response to climate system changes. Total SLV can be observed by radar altimetry satellites such as TOPEX/POSEIDON and Jason 1/2. The steric SLV can be computed through temperature and salinity profiles from in situ measurements or from ocean general circulation models (OGCM), which can assimilate the said observations. The mass-induced SLV can be estimated from its time-variable gravity (TVG) signals. We revisit this problem in the Mediterranean Sea estimating the observed, steric, and mass-induced SLV, for the latter we analyze the latest TVG data set from the GRACE (Gravity Recovery and Climate Experiment) satellite mission launched in 2002, which is 3.5 times longer than in previous studies, with the application of a two-stage anisotropic filter to reduce the noise in high-degree and -order spherical harmonic coefficients. We confirm that the intra-annual total SLV are only produced by water mass changes, a fact explained in the literature as a result of the wind field around the Gibraltar Strait. The steric SLV estimated from the residual of "altimetry minus GRACE" agrees in phase with that estimated from OGCMs and in situ measurements, although showing a higher amplitude. The net water fluxes through both the straits of Gibraltar and Sicily have also been estimated accordingly.

  20. OXIDATION OF CYCLOHEXANE WITH AIR CATALYZED BY A STERICALLY HINDERED IRON (II) COMPLEX

    EPA Science Inventory

    Oxidation of Cyclohexane with Air Catalyzed by a Sterically Hindered Iron(II) Complex.


    Thomas M. Becker, Michael A. Gonzalez*

    United States Environmental Protection Agency; National Risk Management Research Laboratory; Sustainable Technology Division; Clean Pr...

  1. Importance of steric effects on the efficiency and fidelity of transcription by T7 RNA polymerase.

    PubMed

    Ulrich, Sébastien; Kool, Eric T

    2011-11-29

    DNA-dependent RNA polymerases such as T7 RNA polymerase (T7 RNAP) perform the transcription of DNA into mRNA with high efficiency and high fidelity. Although structural studies have provided a detailed account of the molecular basis of transcription, the relative importance of factors like hydrogen bonds and steric effects remains poorly understood. We report herein the first study aimed at systematically probing the importance of steric and electrostatic effects on the efficiency and fidelity of DNA transcription by T7 RNAP. We used synthetic nonpolar analogues of thymine with sizes varying in subangstrom increments to probe the steric requirements of T7 RNAP during the elongation mode of transcription. Enzymatic assays with internal radiolabeling were performed to compare the efficiency of transcription of modified DNA templates with a natural template containing thymine as a reference. Furthermore, we analyzed effects on the fidelity by measuring the composition of RNA transcripts by enzymatic digestion followed by two-dimensional thin layer chromatography separation. Our results demonstrate that hydrogen bonds play an important role in the efficiency of transcription but, interestingly, do not appear to be required for faithful transcription. Steric effects (size and shape variations) are found to be significant both in insertion of a new RNA base and in extension beyond it.

  2. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    PubMed Central

    Tanabe, Nobutake; Tannna, Akio; Konishi, Yohei; Takahashi, Takashi

    2013-01-01

    Summary Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers. PMID:24367397

  3. The applicapility of the steric height criteria of the Antarctic Circumpolar Current jets

    NASA Astrophysics Data System (ADS)

    Tarakanov, Roman

    2016-04-01

    According to the steric height criteria of the jets of the Antarctic Circumpolar Current (ACC) the cores of these jets are kept in time and in a whole circumpolar circle at the same isolines of the steric height. The applicability of these criteria was analyzed on the basis of two databases. The first one is the data of several hydrophysical sections carried out south of Africa which were executed in 2004-2010 along the same track. The second one is the series of daily digital maps of the sea level anomaly (SLA) published by the French CLS agency (www.aviso.oceanobs.com). The analysis was executed by comparing two types of curves along the track. The first one is the differences in the steric heights at the same points between two sections. The second one is the differences in SLA at the same points. The analysis revealed an example of a lack of geometric similarity of these curves for the sections in December 2009 and October 2010 in the southern half of the ACC. This lack is up to 10 cm in the SLA values. This fact points to inapplicability of the steric height criteria of the ACC jets in general. In the other words there is no permanent no-motion surface (depth) in the ACC even in time.

  4. Effect of sterically demanding substituents on the conformational stability of the collagen triple helix.

    PubMed

    Erdmann, Roman S; Wennemers, Helma

    2012-10-17

    The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.

  5. Strategies to overcome statin intolerance.

    PubMed

    Agouridis, Aris P; Nair, Devaki R; Mikhailidis, Dimitri P

    2015-06-01

    This editorial discusses several options to overcome statin intolerance in clinical practice. For example, switching to a different statin, changing statin dosing, using lipid-lowering drugs other than statins (e.g., ezetimibe, bile acid sequestrants and fibrates, alone or in combination), or combining statins with other lipid-lowering drugs. The authors focus on the potential mechanisms involved in statin-related myopathy. New lipid-lowering drugs currently in development (e.g., cholesterol ester transfer protein inhibitors [anacetrapib] and proprotein convertase subtilisin/kexin 9 inhibitors) inhibitors may help in the management of statin intolerance while achieving low-density lipoprotein cholesterol targets as set out by the guidelines.

  6. Separating steric sea level and ocean bottom pressure in the Tropical Asian Seas

    NASA Astrophysics Data System (ADS)

    Kleinherenbrink, M.; Riva, R.; Frederikse, T.

    2016-12-01

    Direct observations of Ocean Bottom Pressure (OBP) in the Tropical Asian Seas (TAS) are normally avoided due to a cut-off of typically 300 km in GRACE gravity fields from the coast to limit hydrological leakage.The limited number of temperature and salinity observations lead to interpolation problems and make it difficult to infer steric changes in the region.To close the sea level budget in the tropical ocean using Argo, GRACE and altimetry, the TAS area is therefore omitted (Von Schuckmann et al., 2014).However, due to its large sea level trends, the omission of the TAS in global sea level budgets leads to an underestimation of 0.5 mm/yr between 2005-2011 (Von Schuckmann et al., 2014).Furthermore, no studies exist to date that separate total sea level into the steric and OBP components, which in combination with large bathymetry fluctuations, hampers the understanding of the dynamics causing interannual variability in sea level in the area. We separate the steric and OBP components in the TAS, using altimetry, optimally filtered ITSG-Grace2016 gravity fields and temperature and salinity grids from various ocean reanalyses.By combining the observations from the three sources in a statistically optimal way, we aim to get the best separation of OBP and steric sea level.The sum of the OBP and steric sea level trends is statistically equal to trend differences caused by omitting the TAS, which makes it possible to correct global sea level budgets.Secondly, the interannual variability is mostly captured by regression with the El-Nino Southern Oscillation (ENSO) 3.4 index.In the deeper regions of the TAS this is primarily a steric signal, however in the shallow areas the interannual signal is of OBP origin.Finally, a large fraction of the OBP trends in the TAS region is explained by trends derived from fingerprints of Greenland, Anarctic, and glacier melt as well as dam retention and land hydrology plus a contribution of the nodal cycle.However, especially in the

  7. Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

    NASA Technical Reports Server (NTRS)

    Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

    1990-01-01

    The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

  8. Steric stabilization of nonaqueous silicon slips. I - Control of particle agglomeration and packing. II - Pressure casting of powder compacts

    NASA Technical Reports Server (NTRS)

    Kerkar, Awdhoot V.; Henderson, Robert J. M.; Feke, Donald L.

    1990-01-01

    The application of steric stabilization to control particle agglomeration and packing of silicon powder in benzene and trichloroethylene is reported. The results provide useful guidelines for controlling unfavorable particle-particle interactions during nonaqueous processing of silicon-based ceramic materials. The application of steric stabilization to the control and improvement of green processing of nonaqueous silicon slips in pressure consolidation is also demonstrated.

  9. Barriers to Asthma Management as Identified by School Nurses

    ERIC Educational Resources Information Center

    Quaranta, Judith E.; Spencer, Gale A.

    2016-01-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors,…

  10. Barriers to Asthma Management as Identified by School Nurses

    ERIC Educational Resources Information Center

    Quaranta, Judith E.; Spencer, Gale A.

    2016-01-01

    Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors,…

  11. Epidermal Barriers

    PubMed Central

    Natsuga, Ken

    2014-01-01

    The epidermis functions as a physical barrier to the external environment and works to prevent loss of water from the skin. Numerous factors have been implicated in the formation of epidermal barriers, such as cornified envelopes, corneocytes, lipids, junctional proteins, proteases, protease inhibitors, antimicrobial peptides, and transcription factors. This review illustrates human diseases (ichthyoses) and animal models in which the epidermal barrier is disrupted or dysfunctional at steady state owing to ablation of one or more of the above factors. These diseases and animal models help us to understand the complicated mechanisms of epidermal barrier formation and give further insights on epidermal development. PMID:24692192

  12. Vehicle barrier

    DOEpatents

    Hirsh, Robert A.

    1991-01-01

    A vehicle security barrier which can be conveniently placed across a gate opening as well as readily removed from the gate opening to allow for easy passage. The security barrier includes a barrier gate in the form of a cable/gate member in combination with laterally attached pipe sections fixed by way of the cable to the gate member and lateral, security fixed vertical pipe posts. The security barrier of the present invention provides for the use of cable restraints across gate openings to provide necessary security while at the same time allowing for quick opening and closing of the gate areas without compromising security.

  13. Role of the lipase-specific foldase of Burkholderia glumae as a steric chaperone.

    PubMed

    El Khattabi, M; Van Gelder, P; Bitter, W; Tommassen, J

    2000-09-01

    Most lipases of Gram-negative bacteria require a lipase-specific foldase (Lif) in order to fold in the periplasm into their active, protease-resistant conformation prior to their secretion. The periplasmic domain of the Lif (amino acids 44-353) of Burkholderia glumae was purified as a His-tagged protein, and its function in the folding of lipase was studied in vitro. Refolding of the denatured lipase into its active conformation was dependent on the presence of the Lif. Circular dichroism revealed that the lipase refolded in the absence of Lif into a form with a native-like conformation, which was more stable against heat-induced denaturation than the native form, but was enzymatically inactive. This form of the protein could be activated by adding Lif after several hours, which demonstrates that the function of this chaperone is to help lipase to overcome an energetic barrier in the productive folding pathway rather than to prevent it from entering a non-productive pathway. The Lif was shown to interact with the native lipase in protease-protection experiments as well as by affinity chromatography, consistent with a role of the Lif late in the folding process. These results demonstrate that the Lif functions in a way analogous to the propeptides of many bacterial proteases and indicate that the amino acid sequence of the lipase does not contain all the information required for the protein to adopt its three-dimensional structure.

  14. Overcoming immunosuppression in bone metastases.

    PubMed

    Reinstein, Zachary Z; Pamarthy, Sahithi; Sagar, Vinay; Costa, Ricardo; Abdulkadir, Sarki A; Giles, Francis J; Carneiro, Benedito A

    2017-09-01

    Bone metastases are present in up to 70% of advanced prostate and breast cancers and occur at significant rates in a variety of other cancers. Bone metastases can be associated with significant morbidity. The establishment of bone metastasis activates several immunosuppressive mechanisms. Hence, understanding the tumor-bone microenvironment is crucial to inform the development of novel therapies. This review describes the current standard of care for patients with bone metastatic disease and novel treatment options targeting the microenvironment. Treatments reviewed include immunotherapies, cryoablation, and targeted therapies. Combinatorial treatment strategies including targeted therapies and immunotherapies show promise in pre-clinical and clinical studies to overcome the suppressive environment and improve treatment of bone metastases. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Overcoming "the Valley of Death".

    PubMed

    McIntyre, Robin A

    2014-01-01

    On a global level there are major challenges arising from climate change, resource use and changing age demographics. These issues have created a global marketplace for novel innovative products and solutions which can help to combat and overcome these challenges which have created significant commercial opportunities for companies, particularly for small and medium size enterprises or SMEs. Companies most likely to take advantage of these opportunities will be those which can innovate in a timely manner. Innovation significantly contributes to higher productivity and economic growth, and is core to a company's competitiveness within often challenging marketplaces. However, many factors can stifle innovation. Companies can struggle to identify finance for early-stage development, the returns can be difficult to predict, and the innovation 'landscape' is often complex and unclear. This brief review describes some of the main issues with commercialising innovative ideas and provides guidance with respect to the often complicated funding landscape both on a National and European level.

  16. Overcoming challenges in improvement work.

    PubMed

    Crisp, Helen

    2013-09-01

    The Health Foundation is an independent charity working to improve healthcare in the UK, so that we have a system of the highest possible quality-safe, effective, person-centred, timely, efficient and equitable. We believe that in order to achieve this, health services need to continually improve the way they work. The Foundation conducts research and evaluation, puts ideas into practice through improvement programmes, develops leaders and shares evidence to drive wider change. The work is a focused around two priority areas: patient safety and person-centred care. The Foundation has supported work to improve services for patients with kidney disease and, in common with other quality improvement projects, there have been challenges to overcome. Awareness of these common challenges can help others to be more prepared when planning service improvements. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  17. Influence of ion sterics on diffusiophoresis and electrophoresis in concentrated electrolytes

    NASA Astrophysics Data System (ADS)

    Stout, Robert F.; Khair, Aditya S.

    2017-01-01

    We quantify the diffusiophoresis and electrophoresis of a uniformly charged, spherical colloid in a binary electrolyte using modified Poisson-Nernst-Planck equations that account for steric repulsion between finite sized ions. Specifically, we utilize the Bikerman (Bik) lattice gas model and the Carnahan-Starling (CS) and Boublik-Mansoori-Carnahan-Starling-Leland (BMCSL) equations of state for monodisperse and polydisperse, respectively, hard spheres. We compute the phoretic mobility for weak applied fields using an asymptotic approach for thin diffuse layers, where ion steric effects are expected to be most prevalent. The thin diffuse layer limit requires λD/R →0 , where λD is the Debye screening length and R is the particle radius; this limit is readily attained for micron-sized colloids in concentrated electrolytic solutions. It is well known that the classic Poisson-Boltzmann (PB) model for pointlike, noninteracting ions leads to a prediction of a maximum in both the diffusiophoretic and electrophoretic mobilities with increasing particle zeta potential (at fixed λD/R ). In contrast, we find that ion sterics essentially eliminate this maximum (for reasonably attainable zeta potentials) and increase the mobility relative to PB. Next, we consider the more experimentally relevant case of a particle with a constant surface charge density and vary the electrolyte concentration, neglecting charge regulation on surface active sites. Rather surprisingly, there is little difference between the predictions of the four models (PB, Bik, CS, and BMCSL) for electrophoretic mobility in concentrated solutions, at reasonable surface charge densities (˜1 -10 μ C /cm2 ). This is because as the concentration increases, the zeta potential is reduced (to below the thermal voltage for concentrations above about 1 M) and therefore the diffuse layer structure is largely unaffected by ion sterics. For gradients of symmetric electrolytes (equal diffusivities, charge, and size

  18. Structural peculiarities of configurational isomers of 1-styrylpyrroles according to 1Н, 13С and 15N NMR spectroscopy and density functional theory calculations: electronic and steric hindrance for planar structure.

    PubMed

    Afonin, Andrei V; Ushakov, Igor A; Pavlov, Dmitry V; Schmidt, Elena Yu; Dvorko, Marina Yu

    2013-06-01

    Comparative analysis of the (1)Н and (13)С NMR data for a series of the E and Z-1-styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene suggests that the conjugation between the unsaturated fragments in the former compounds is reduced. This is the result of the mutual influence of the donor p-π and π-π conjugation having opposite directions. According to the NMR data combined with the density functional theory calculations, the Z isomer of 1-styrylpyrrole has essentially a nonplanar structure because of the steric hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane structure despite the absence of a sterical barrier for the planar one. Deviation of the E isomer from the planar structure seems to be caused by an electronic hindrance produced by a mutual influence of the p-π and π-π conjugation. The structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral angle between planes of the pyrrole ring and double bond. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Steric vs electronic effects in binary uranyl alkoxides: A spectroscopic perspective

    NASA Astrophysics Data System (ADS)

    Morris, David E.; Wilkerson, Marianne P.; Burns, Carol J.; Scott, Brian L.; Wilkerson, Marianne P.; Paine, Robert T.

    2000-07-01

    Recent advances in the non-aqueous alkoxide chemistry of UO22+ have provided the wherewithal to prepare and isolate a broad range of discrete molecular uranyl entities both as solids and in aprotic solvents in which it is possible to tune the ligand basicity and steric encumbrance. Uranyl complexes have been isolated as monomers, dimers, and higher order oligomers. These complexes afford an opportunity to examine in some detail the relative importance of ligand basicity and steric demand in directing structural preferences (monomer vs. dimer, cis vs. trans isomers) and in determining electronic structural properties and relative bond strengths in the "yl" and equatorial bonds. In the present report the electronic and vibrational spectroscopic data for a series of uranyl alkoxides are correlated with molecular structural data to examine trends in electronic structure and bonding and compare these results with existing models based on the more classical uranyl coordination compounds.

  20. Using steric hindrance to design new inhibitors of class C beta-lactamases

    SciTech Connect

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K.

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  1. Steric effect in the energy transfer reaction of Ar(3P2)+N2

    NASA Astrophysics Data System (ADS)

    Watanabe, D.; Ohoyama, H.; Matsumura, T.; Kasai, T.

    2006-08-01

    Steric effect for N2(C,Πu3) formation in the energy transfer reaction of Ar(P23)+N2 was directly measured by using an oriented Ar(P23,MJ=2) beam at a collision energy of 0.06eV. The N2(C,Πu3) chemiluminescence intensity was measured as a function of the magnetic orientation field direction in the collision frame. A significant alignment effect on the energy transfer probability was observed. The relative reactivity for each magnetic substate in the collision frame σ∣MJ'∣ was determined to be σ∣2∣:σ∣1∣:σ0=0.50:0.60:1.00. It is suggested that the observed steric effect is primarily due to the favorable configuration of the 3p orbital for the efficient overlap with the 2σu molecular orbital of N2.

  2. Electrocatalytic Alcohol Oxidation with TEMPO and Bicyclic Nitroxyl Derivatives: Driving Force Trumps Steric Effects.

    PubMed

    Rafiee, Mohammad; Miles, Kelsey C; Stahl, Shannon S

    2015-11-25

    Bicyclic nitroxyl derivatives, such as 2-azaadamantane N-oxyl (AZADO) and 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), have emerged as highly effective alternatives to TEMPO-based catalysts for selective oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-1-piperidine N-oxyl). Their efficacy is widely attributed to their smaller steric profile; however, electrocatalysis studies described herein show that the catalytic activity of nitroxyls is more strongly affected by the nitroxyl/oxoammonium redox potential than by steric effects. The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols. Mechanistic studies provide insights into the origin of these unexpected reactivity trends. The superior activity of ACT is especially noteworthy at high pH, where bicyclic nitroxyls are inhibited by formation of an oxoammonium hydroxide adduct.

  3. Ion-Conserving Modified Poisson-Boltzmann Theory Considering a Steric Effect in an Electrolyte

    NASA Astrophysics Data System (ADS)

    Sugioka, Hideyuki

    2016-12-01

    The modified Poisson-Nernst-Planck (MPNP) and modified Poisson-Boltzmann (MPB) equations are well known as fundamental equations that consider a steric effect, which prevents unphysical ion concentrations. However, it is unclear whether they are equivalent or not. To clarify this problem, we propose an improved free energy formulation that considers a steric limit with an ion-conserving condition and successfully derive the ion-conserving modified Poisson-Boltzmann (IC-MPB) equations that are equivalent to the MPNP equations. Furthermore, we numerically examine the equivalence by comparing between the IC-MPB solutions obtained by the Newton method and the steady MPNP solutions obtained by the finite-element finite-volume method. A surprising aspect of our finding is that the MPB solutions are much different from the MPNP (IC-MPB) solutions in a confined space. We consider that our findings will significantly contribute to understanding the surface science between solids and liquids.

  4. Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact.

    PubMed

    Shaw, Paul; Kennedy, Alan R; Nelson, David J

    2016-08-07

    The synthesis and co-ordination chemistry of a new 'bulky yet flexible' N-heterocyclic carbene ("IPaul") is reported. This carbene has spatially-defined steric impact; steric maps show that two quadrants are very bulky while the other two are quite open. The electronic properties of this carbene are very similar to those of other 1,3-diarylimidazol-2-ylidenes. Copper, silver, iridium, and nickel complexes of the new ligand have been prepared. In solution, the ligand adopts two different conformations, while X-ray crystallographic analyses of the transition metal complexes suggest that the syn-conformer is preferred in the solid state due to intermolecular interactions. The copper(i) chloride complex of this new ligand has been shown to be highly-active in the hydrosilylation of carbonyl compounds, when compared to the analogous IPr, IMes, IPr* and IPr*(OMe) complexes.

  5. Tuning steric and electronic effects in transition-metal β-diketiminate complexes

    PubMed Central

    Chen, Chi; Bellows, Sarina M.; Holland, Patrick L.

    2015-01-01

    β-Diketiminates are widely used supporting ligands for building a range of metal complexes with different oxidation states, structures, and reactivities. This Perspective summarizes the steric and electronic influences of ligand substituents on these complexes, with an eye toward informing the design of new complexes with optimized properties. The backbone and N-aryl substituents can give significant steric effects on structure, reactivity and selectivity of reactions. The electron density on the metal can be tuned by installation of electron withdrawing or donating groups on the β-diketiminate ligand as well. Examples are shown from throughout the transition metal series to demonstrate different types of effects attributable to systematic variation of β-diketiminate ligands. PMID:26244489

  6. The molecular electrostatic potential and steric accessibility of A-DNA.

    PubMed Central

    Lavery, R; Pullman, B

    1981-01-01

    The molecular electrostatic potential and steric accessibility of A-DNA are computed for base sequences (dG.dC)n and (dA.dT)n. An interpretation of the results in terms of the structure of A-DNA is provided and differences with respect to other forms of DNA, namely B-DNA and Z-DNA, are discussed. PMID:7301586

  7. Structure of a membrane-based steric chaperone in complex with its lipase substrate.

    PubMed

    Pauwels, Kris; Lustig, Ariel; Wyns, Lode; Tommassen, Jan; Savvides, Savvas N; Van Gelder, Patrick

    2006-04-01

    Secretion via the type II secretion pathway in Gram-negative bacteria often relies crucially on steric chaperones in the periplasm. Here, we report the crystal structure of the soluble form of a lipase-specific foldase (Lif) from Burkholderia glumae in complex with its cognate lipase. The structure reveals how Lif uses a novel alpha-helical scaffold to embrace lipase, thereby creating an unusually extensive folding platform.

  8. Stereoelectronic, torsional, and steric effects on rates of enolization of ketones.

    PubMed

    Behnam, S M; Behnam, S E; Ando, K; Green, N S; Houk, K N

    2000-12-29

    The stereoselectivities of base-catalyzed enolizations of ketones have been studied by quantum mechanical methods. Transition structures of exo and endo deprotonation of camphor, norcamphor, and dehydronorcamphor have been located with two model bases. Stereoelectronic, torsional, and steric effects on activation energies were assessed. These calculations demonstrate the importance of torsional strain between partial bonds and vicinal bonds on the rates of deprotonation and on related reactions involving the formation of enolates or reactions of enols and enolates.

  9. Chromatography Models with Langmuir and Steric Mass Action Adsorption Isotherms are of Differential Index One

    NASA Astrophysics Data System (ADS)

    von Lieres, Eric

    2010-09-01

    Chromatography is commonly applied for the separation of bio-molecules in pharmaceutical industry, and chromatography models are increasingly applied for rational process analysis and optimization. A rapid equilibrium assumption is often applied for the adsorption equation, which results in a non-linear system of partial differential-algebraic equations (PDAEs). In this contribution a proof is given, that these PDAEs are of differential index one for the two most prominent isotherm models, Langmuir and steric mass action (SMA).

  10. Exclusive formation of monovalent quantum dot imaging probes by steric exclusion

    PubMed Central

    Farlow, Justin; Seo, Daeha; Broaders, Kyle E.; Taylor, Marcus; Gartner, Zev J.; Jun, Young-wook

    2013-01-01

    Precise control over interfacial chemistry between nanoparticles and other materials remains a significant challenge limiting the broad application of nanotechnology in biology. To address this challenge, we use “Steric Exclusion” to completely convert commercial quantum dots (QDs) into monovalent imaging probes by wrapping the QD with a functionalized oligonucleotide. We demonstrate the utility of these QDs as modular and non-perturbing imaging probes by tracking individual Notch receptors on live cells. PMID:24122039

  11. Bioenergetic Progress and Heat Barriers

    NASA Astrophysics Data System (ADS)

    Zotin, A. A.; Lamprecht, I.; Zotin, A. I.

    2001-07-01

    Progressing biological evolution is discussed in the framework of nonequilibrium thermodynamics. It is connected with an increase of the mass specific standard metabolism given by coefficient a in the allometric relation (1) between oxygen consumption rate and body mass of an animal. Three “heat barriers” are found in the course of such a bioenergetic evolution. The first heat barrier concerns an animal's overheating during active movement and is overcome by the development of thermoregulation and the appearance of homeothermic animals. A second barrier arises when the coefficient a reaches values connected with lethal body temperatures. The transition across this second heat barrier occurs as result of reasonable activities and the appearance of civilization. The third heat barrier will arise during the further development of human civilization, connected with a highly increased energy production and a fatal warming of the Earth atmosphere. The manner to overcome this barrier will probably depend on the assimilation of space and the establishment of energy consuming industries outside the Earth. The bioenergetic evolution discussed in this paper does not exclude other trends of evolution, e.g. increase of size, and does not mean to be the only aspect of biological evolution.

  12. Dynamical properties of steric zipper polymorphs formed by a IAPP-derived peptide.

    PubMed

    Stanzione, Francesca; De Simone, Alfonso; Esposito, Luciana; Vitagliano, Luigi

    2012-08-01

    Understanding the molecular basis of neurodegenerative diseases has enormous implications for the development of effective therapeutic strategies. One of the most puzzling features of these pathologies is the occurrence of distinct strains, which are believed to be generated by alternative conformational transitions of the same protein/peptide. Very recently, it has been discovered that small model peptides are able to form alternative tightly packed assemblies (polymorphs) in the crystalline state. Intriguingly, it has been postulated that the different polymorphs of the same polypeptide sequence may be representative of distinct strains. As the organization of crystalline aggregates of small peptides may be heavily biased by crystal packing, we have here performed MD simulations on steric zipper polymorphs formed by of the IAPP-derived fragment SSTNVG. Our analyses show that these aggregates are rather stable also in a non-crystalline environment. This finding corroborates the hypothesis that steric zipper assemblies are good candidates to account for the phenomenon of strain in neurodegenerative diseases. Present investigations also provide clues on the factors that favour the formation of polymorphs. Indeed, the intrinsic stability of individual β-sheets formed by SSTNVG strands is very poor. Therefore, the formation of these aggregates is essentially dictated by inter-sheet interactions established within the steric zipper assembly.

  13. Steric and Mass-Induced Sea Level Variations in the Mediterranean Sea, Revisited

    NASA Astrophysics Data System (ADS)

    Garcia-Garcia, D.; Chao, B. F.; Boy, J.-P.

    2009-04-01

    Observed by radar altimetry satellites such as TOPEX/Poseidon (T/P) and Jason-1/2, the total Sea Level Variations (SLV) are produced by a combination of the steric and mass-induced components. The steric SLV can be computed from in situ measurements of temperature and salinity profiles, or from Ocean General Circulation Models (OGCM) that can assimilate those measurements. Mass-induced SLV can be estimated, since 2002, from Time-Variable Gravity (TVG) measurements by the GRACE satellite mission. This methodology has been successfully applied in estimation of the global ocean mass-induced SLV. However, some difficulties arise when studying semi-enclosed basins due to land aliasing of the GRACE TVG signal. The problem is specially complicated in the Mediterranean Sea as reported in previous studies. We revisit this problem analyzing release 4 of the GRACE data set, which represents a time series 3 times longer than in previous studies, by means of new and more efficient filters to reduce the noise in the high degree and order spherical harmonics coefficients. The seasonal and non-seasonal signals are analyzed. From the comparison of GRACE with altimetry data a general underestimation of the steric term is observed in the OGCMs used.

  14. Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures.

    PubMed

    Yue, Yuan; Li, Guoli; Yang, Yun; Zhang, Wenjing; Pan, Huawei; Chen, Ran; Shi, Feng; Jin, Yongfeng

    2013-12-01

    The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016 distinct isoforms in Drosophila melanogaster via mutually exclusive splicing. Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually exclusive splicing through steric hindrance in combination with RNA secondary structure. This mutually exclusive behavior is enforced by steric hindrance, due to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA structures are evolutionarily conserved in 36 non-Drosophila species of six distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera, Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants via masking the splice site. By contrast, a previously uncharacterized RNA structure specifically activated exon 17.1 by bringing splice sites closer together in Drosophila, while the other moderately suppressed exon 17.1 selection by hindering the accessibility of polypyrimidine sequences. Taken together, these data suggest a phylogeny of increased complexity in regulating alternative splicing of Dscam exon 17 spanning more than 300 million years of insect evolution. These results also provide models of the regulation of alternative splicing through steric hindrance in combination with dynamic structural codes.

  15. Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures

    PubMed Central

    Yue, Yuan; Li, Guoli; Yang, Yun; Zhang, Wenjing; Pan, Huawei; Chen, Ran; Shi, Feng; Jin, Yongfeng

    2013-01-01

    The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016 distinct isoforms in Drosophila melanogaster via mutually exclusive splicing. Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually exclusive splicing through steric hindrance in combination with RNA secondary structure. This mutually exclusive behavior is enforced by steric hindrance, due to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA structures are evolutionarily conserved in 36 non-Drosophila species of six distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera, Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants via masking the splice site. By contrast, a previously uncharacterized RNA structure specifically activated exon 17.1 by bringing splice sites closer together in Drosophila, while the other moderately suppressed exon 17.1 selection by hindering the accessibility of polypyrimidine sequences. Taken together, these data suggest a phylogeny of increased complexity in regulating alternative splicing of Dscam exon 17 spanning more than 300 million years of insect evolution. These results also provide models of the regulation of alternative splicing through steric hindrance in combination with dynamic structural codes. PMID:24448213

  16. Parameterization of phosphine ligands demonstrates enhancement of nickel catalysis via remote steric effects

    NASA Astrophysics Data System (ADS)

    Wu, Kevin; Doyle, Abigail G.

    2017-08-01

    The field of Ni-catalysed cross-coupling has seen rapid recent growth because of the low cost of Ni, its earth abundance, and its ability to promote unique cross-coupling reactions. Whereas advances in the related field of Pd-catalysed cross-coupling have been driven by ligand design, the development of ligands specifically for Ni has received minimal attention. Here, we disclose a class of phosphines that enable the Ni-catalysed Csp3 Suzuki coupling of acetals with boronic acids to generate benzylic ethers, a reaction that failed with known ligands for Ni and designer phosphines for Pd. Using parameters to quantify phosphine steric and electronic properties together with regression statistical analysis, we identify a model for ligand success. The study suggests that effective phosphines feature remote steric hindrance, a concept that could guide future ligand design tailored to Ni. Our analysis also reveals that two classic descriptors for ligand steric environment—cone angle and % buried volume—are not equivalent, despite their treatment in the literature.

  17. Steric confinement of proteins on lipid membranes can drive curvature and tubulation.

    PubMed

    Stachowiak, Jeanne C; Hayden, Carl C; Sasaki, Darryl Y

    2010-04-27

    Deformation of lipid membranes into curved structures such as buds and tubules is essential to many cellular structures including endocytic pits and filopodia. Binding of specific proteins to lipid membranes has been shown to promote membrane bending during endocytosis and transport vesicle formation. Additionally, specific lipid species are found to colocalize with many curved membrane structures, inspiring ongoing exploration of a variety of roles for lipid domains in membrane bending. However, the specific mechanisms by which lipids and proteins collaborate to induce curvature remain unknown. Here we demonstrate a new mechanism for induction and amplification of lipid membrane curvature that relies on steric confinement of protein binding on membrane surfaces. Using giant lipid vesicles that contain domains with high affinity for his-tagged proteins, we show that protein crowding on lipid domain surfaces creates a protein layer that buckles outward, spontaneously bending the domain into stable buds and tubules. In contrast to previously described bending mechanisms relying on local steric interactions between proteins and lipids (i.e. helix insertion into membranes), this mechanism produces tubules whose dimensions are defined by global parameters: domain size and membrane tension. Our results suggest the intriguing possibility that confining structures, such as lipid domains and protein lattices, can amplify membrane bending by concentrating the steric interactions between bound proteins. This observation highlights a fundamental physical mechanism for initiation and control of membrane bending that may help explain how lipids and proteins collaborate to create the highly curved structures observed in vivo.

  18. Barriers to cancer screening.

    PubMed

    Womeodu, R J; Bailey, J E

    1996-01-01

    Many barriers to cancer screening have been summarized and discussed. Barriers have been documented in all patient populations, but some groups such as ethnic minorities and the elderly face unique barriers. The barriers to cancer screening, are multifactorial, but much of the responsibility for change must lie with health care providers and the health care delivery industry. This is not to free the patient of all responsibility, but some significant barriers are beyond their direct control. Take, for example, socioeconomic status, disease knowledge, and culturally related perceptions and myths about cancer detection and treatment. The health care industry must do a better job identifying and overcoming these barriers. The significant effects of provider counseling and advice must not be underestimated. Patients must first be advised, and then further actions must be taken if they reject the screening advice. Did they refuse adherence to recommendations because they do not view themselves as susceptible, because of overwhelming personal barriers, or because of a fatalistic attitude toward cancer detection and treatment? If that is the case, physicians and health care institutions must attempt to change perceptions, educate, and personalize the message so that patients accept their disease susceptibility [table: see text]. Multiple patient and provider risk factors have been identified that can be used to target patients particularly at high risk for inadequate cancer screening and providers at high risk for performing inadequate screening. Research has clearly demonstrated the effectiveness of interventions to improve tracking of patient and physician compliance with screening recommendations. Further research is needed to show the impact of managed-care penetration and payer status on screening efforts, and incentive schemes need to be tested that reward institutions and third-party payers who develop uniform standards and procedures for cancer screening. The

  19. Glucocorticosteroids in Nano-Sterically Stabilized Liposomes Are Efficacious for Elimination of the Acute Symptoms of Experimental Cerebral Malaria

    PubMed Central

    Waknine-Grinberg, Judith H.; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K.; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage. PMID:23991146

  20. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria.

    PubMed

    Waknine-Grinberg, Judith H; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Golenser, Jacob; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage.

  1. Synthesis of sterically hindered ortho-substituted tetraphenylethenes. Electronic effects in the McMurry olefination reaction.

    PubMed

    Chung, Mee-Kyung; Qi, Guizhong; Stryker, Jeffrey M

    2006-03-30

    [reaction: see text] Contrary to literature consensus, the McMurry olefination reaction can be extended to the direct synthesis of sterically encumbered tetrakis(2-substituted) tetraphenylethenes from the corresponding 2,2'-disubstituted benzophenones. The reaction exploits previously unrecognized substrate-based electronic effects that dominate over otherwise controlling steric considerations and provides highly efficient access to derivatives of tetrakis(2-hydroxyphenyl)ethene, a novel preorganized ligand system for polymetallic coordination chemistry and catalysis.

  2. Math Is Like a Scary Movie? Helping Young People Overcome Math Anxiety

    ERIC Educational Resources Information Center

    Kulkin, Margaret

    2016-01-01

    Afterschool teachers who tutor students or provide homework help have a unique opportunity to help students overcome the social or emotional barriers that so often block learning. They can embrace a creative and investigative approach to math learning. Margaret Kulkin's interest in being a math attitude "myth-buster" led her to apply to…

  3. Steric sea level change in the Bay of Bengal: investigating the most variable component of sea level change

    NASA Astrophysics Data System (ADS)

    Uebbing, Bernd; Kusche, Jürgen; Rietbroek, Roelof; Shum, Ck

    2015-04-01

    Regional sea level change is influenced by contributions from mass sources, like melting of glaciers and the ice-sheets in Greenland and Antarctica, as well as steric contributions from changes in temperature and salinity of the oceans. Radar altimetry indicates a sea level trend in the Bay of Bengal of about 6 mm- yr over the time period of 2002-2014, which is significantly larger than the global mean trend. Here, we explain 80% of this rise by steric contributions and 20% by mass-related contributions. The increased rise of sea level in the Bay of Bengal threatens the coastal vulnerability of the surrounding countries like Bangladesh, where this effect is exacerbated in combination with land subsidence of the very low lying coastal areas. The BanD-AID (Bangladesh Delta: Assessment of the Causes of Sea-level Rise Hazards and Integrated Development of Predictive Modeling Towards Mitigation and Adaptation) project tries to assess the current and future sea level rise and its impacts on the people living in the threatened coastal areas. As a part of this, it is necessary to analyze the different mass and steric contributors to the total sea level rise to aid in the prediction of future risks. We use data from radar altimetry and the GRACE mission to separate the total sea level rise into contributions from mass sources and steric changes. In our approach, temporal GRACE gravity data and Jason-1 and -2 along track altimetry data are fitted to time invariant spatial patterns (fingerprints) to avoid problems with GRACE resolution, filtering, geocenter and related issues. Our results show that in the Bay of Bengal the steric component is influenced by annual and interannual phenomena and, at the same time, it is significantly larger compared to the individual mass contributions, which show a linear and relatively stable behavior over time. We validate the steric component of our inversion by comparing it to independent steric estimates from 4-D gridded temperature and

  4. Diisocyanate modified graphene oxide network structure: steric effect of diisocyanates on bimolecular cross-linking degree

    NASA Astrophysics Data System (ADS)

    Saha, Uttam; Jaiswal, Rimpa; Singh, Jyoti Prakash; Goswami, Thako Hari

    2014-05-01

    Relative reactivity and the extent of functionalization of graphene oxide (GO) during its bimolecular reaction with three different classes of diisocyanates, i.e., aliphatic (hexamethylene diisocyanate, HMDI), alicyclic (isophorone diisocyanates, IPDI), and aromatic (toluene diisocyanates, TDI), are correlated on the basis of steric and electronic effect of diisocyanate functionalizing agents. The bimolecular reaction produces cross-linked network structure and the steric nature of diisocyanates dominates over electronic factor in regulating the relative reactivity, extent of functionalization and disorder in final structure. Formation of carbamate and amide bonds on participation of GO's sp3-hydroxyl groups at top and bottom of basal plane and sp2-carboxyl groups at the edges are recognized from FTIR and XPS spectra. Extent of functionalization in different locations are predicted from relative ratio of hydroxyl and carboxyl groups participated in diisocyanate reaction and N1s XPS spectra show nearly 3:1, 2:1, 1.3:1 in HMDI, IPDI, and TDI respectively. The disorders in final structure are evaluated by comparing Raman, UV-Vis, and C1s XPS spectra of functionalized materials with GO. TDI, the most sterically hindered diisocyanate among the reported one, shows slowest reactivity and minimum disorder in the final structure compared to long chain aliphatic diisocyanate, HMDI. Depending on the relative participation of oxygenated functional groups at basal and/or edges of two adjacent GO nano sheets, the three possible reaction patterns, i.e., basal to basal, basal to edge, and edge to edge, are proposed. Different crystallographic orientations and out-of-plane arrangement of graphene layers arises from these reactions are correlated through XRD data.

  5. Steric stabilization of Pickering emulsions for the efficient synthesis of polymeric microcapsules.

    PubMed

    Salari, Joris W O; van Heck, Jeroen; Klumperman, Bert

    2010-09-21

    It is commonly known that Pickering emulsions are extremely stable against coalescence and are, therefore, potentially interesting for the synthesis of new materials, such as colloidosomes, microcapsules, composite particles, foams, and so on. However, for the efficient synthesis of such materials, one also has to consider the colloidal stability against aggregation, which is often neglected. In this study, it is demonstrated that steric stabilization is provided to Pickering emulsion droplets by the adsorption of poly(styrene-block-ethylene-co-propylene) (pS-b-EP) and that it is a requirement for the efficient synthesis of polymeric microcapsules. Monodisperse polystyrene particles of 648 nm are synthesized by soap-free emulsion polymerization. A model Pickering emulsion is then formed by the addition of sodium chloride at a critical concentration of 325 mM and mixing it with either heptane or decane. Subsequently, pS-b-EP is added to the Pickering emulsion to provide steric stabilization. Size exclusion chromatography is used to prove and quantify the adsorption of pS-b-EP onto the Pickering emulsion droplets. A maximum surface coverage of 1.3 mg/m(2) is obtained after 2 h, which is approximately one-third of the adsorption on a pure pS surface. We believe that the presence of polar sulfate groups on the particle, which initially stabilized the particle in water, reduces the adsorption of pS-b-EP. Microcapsules are formed by heating the Pickering emulsion above the glass-transition temperature of the particles. Significant aggregation is observed, if no pS-b-EP is used. The adsorption of pS-b-EP provides steric stabilization to the Pickering emulsion droplets, reduces aggregation significantly, and ultimately leads to the successful and efficient synthesis of pS microcapsules.

  6. Steric effects in the dynamics of electrolytes at large applied voltages. I. Double-layer charging

    NASA Astrophysics Data System (ADS)

    Kilic, Mustafa Sabri; Bazant, Martin Z.; Ajdari, Armand

    2007-02-01

    The classical Poisson-Boltzmann (PB) theory of electrolytes assumes a dilute solution of point charges with mean-field electrostatic forces. Even for very dilute solutions, however, it predicts absurdly large ion concentrations (exceeding close packing) for surface potentials of only a few tenths of a volt, which are often exceeded, e.g., in microfluidic pumps and electrochemical sensors. Since the 1950s, several modifications of the PB equation have been proposed to account for the finite size of ions in equilibrium, but in this two-part series, we consider steric effects on diffuse charge dynamics (in the absence of electro-osmotic flow). In this first part, we review the literature and analyze two simple models for the charging of a thin double layer, which must form a condensed layer of close-packed ions near the surface at high voltage. A surprising prediction is that the differential capacitance typically varies nonmonotonically with the applied voltage, and thus so does the response time of an electrolytic system. In PB theory, the differential capacitance blows up exponentially with voltage, but steric effects actually cause it to decrease while remaining positive above a threshold voltage where ions become crowded near the surface. Other nonlinear effects in PB theory are also strongly suppressed by steric effects: The net salt adsorption by the double layers in response to the applied voltage is greatly reduced, and so is the tangential “surface conduction” in the diffuse layer, to the point that it can often be neglected compared to bulk conduction (small Dukhin number).

  7. Long-circulating sterically stabilized liposomes in the treatment of infections.

    PubMed

    Bakker-Woudenberg, Irma A J M; Schiffelers, Raymond M; Storm, Gert; Becker, Martin J; Guo, Luke

    2005-01-01

    The administration of antimicrobial agents encapsulated in long-circulating sterically stabilized liposomes results in a considerable enhancement of therapeutic efficacy compared with the agents in the free form. After liposomal encapsulation, the pharmacokinetics of the antimicrobial agents is significantly changed. An increase in circulation time and reduction in toxic side effects of the agents are observed. In contrast to other types of long-circulating liposomes, an important characteristic of these sterically stabilized liposomes is that their prolonged blood circulation time is, to a high degree, independent of liposome characteristics such as liposome particle size, charge and lipid composition (rigidity) of the bilayer, and lipid dose. This provides the opportunity to manipulate antibiotic release from these liposomes at the site of infection, which is important in view of the differences in pharmacodynamics of different antibiotics and can be done without compromising blood circulation time and degree of target localization of these liposomes. Depending on the liposome characteristics and the agent encapsulated, antibiotic delivery to the infected site is achieved, or the liposomes act as a micro-reservoir function for the antibiotic. In experimental models of localized or disseminated bacterial and fungal infections, the sterically stabilized liposomes have successfully been used to improve antibiotic treatment using representative agents of various classes of antibacterial agents such as the beta-lactams, the aminoglycosides, and the quinolones or the antifungal agent amphotericin B. Extensive biodistribution studies have been performed. Critical factors that contribute to liposome target localization in infected tissue have been elucidated. Liposome-related factors that were investigated were poly(ethylene glycol) density, particle size, bilayer fluidity, negative surface charge, and circulation kinetics. Host-related factors focused on the components

  8. Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

    NASA Astrophysics Data System (ADS)

    Storto, Andrea; Masina, Simona; Balmaseda, Magdalena; Guinehut, Stéphanie; Xue, Yan; Szekely, Tanguy; Fukumori, Ichiro; Forget, Gael; Chang, You-Soon; Good, Simon A.; Köhl, Armin; Vernieres, Guillaume; Ferry, Nicolas; Peterson, K. Andrew; Behringer, David; Ishii, Masayoshi; Masuda, Shuhei; Fujii, Yosuke; Toyoda, Takahiro; Yin, Yonghong; Valdivieso, Maria; Barnier, Bernard; Boyer, Tim; Lee, Tony; Gourrion, Jérome; Wang, Ou; Heimback, Patrick; Rosati, Anthony; Kovach, Robin; Hernandez, Fabrice; Martin, Matthew J.; Kamachi, Masafumi; Kuragano, Tsurane; Mogensen, Kristian; Alves, Oscar; Haines, Keith; Wang, Xiaochun

    2017-08-01

    Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003-2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993-2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread.

  9. Determining the Effective Density and Stabilizer Layer Thickness of Sterically Stabilized Nanoparticles

    PubMed Central

    2016-01-01

    A series of model sterically stabilized diblock copolymer nanoparticles has been designed to aid the development of analytical protocols in order to determine two key parameters: the effective particle density and the steric stabilizer layer thickness. The former parameter is essential for high resolution particle size analysis based on analytical (ultra)centrifugation techniques (e.g., disk centrifuge photosedimentometry, DCP), whereas the latter parameter is of fundamental importance in determining the effectiveness of steric stabilization as a colloid stability mechanism. The diblock copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using RAFT aqueous emulsion polymerization: this approach affords relatively narrow particle size distributions and enables the mean particle diameter and the stabilizer layer thickness to be adjusted independently via systematic variation of the mean degree of polymerization of the hydrophobic and hydrophilic blocks, respectively. The hydrophobic core-forming block was poly(2,2,2-trifluoroethyl methacrylate) [PTFEMA], which was selected for its relatively high density. The hydrophilic stabilizer block was poly(glycerol monomethacrylate) [PGMA], which is a well-known non-ionic polymer that remains water-soluble over a wide range of temperatures. Four series of PGMAx–PTFEMAy nanoparticles were prepared (x = 28, 43, 63, and 98, y = 100–1400) and characterized via transmission electron microscopy (TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). It was found that the degree of polymerization of both the PGMA stabilizer and core-forming PTFEMA had a strong influence on the mean particle diameter, which ranged from 20 to 250 nm. Furthermore, SAXS was used to determine radii of gyration of 1.46 to 2.69 nm for the solvated PGMA stabilizer blocks. Thus, the mean effective density of these sterically stabilized particles was calculated and determined to lie between 1.19 g

  10. Calix[6]azacryptand Ligand with a Sterically Protected Tren-Based Coordination Site for Metal Ions.

    PubMed

    Zahim, Sara; Wickramasinghe, Lasantha A; Evano, Gwilherm; Jabin, Ivan; Schrock, Richard R; Müller, Peter

    2016-04-01

    A new calix[6]azacryptand ligand has been prepared in six steps starting from 1,3,5-trismethoxycalix[6]arene. An X-ray study shows that this ligand has a sterically protected tren-based binding site at the bottom of a polyaromatic bowl and ether sites around its rim. It binds Zn(2+) to give a complex in which zinc is in a trigonal bipyramidal geometry with a water bound in one apical position and two additional hydrogen-bonded waters that fill the calixarene cavity.

  11. Photosensitizer in a molecular bowl: steric protection enhancing the photonuclease activity of copper(II) scorpionates.

    PubMed

    Dhar, Shanta; Chakravarty, Akhil R

    2005-04-18

    Steric encumbrance caused by the tripodal ligand in the ternary tris(3-phenylpyrazolyl)borate copper(II) heterocyclic base complexes [Cu(B)(Tp(Ph))](ClO(4)) (B = dipyridoquinoxaline, dipyridophenazine) leads to efficient cleavage of supercoiled DNA to its relaxed form upon exposure to red light at 632.8 and 694 nm as a result of protection of the photosensitizer in the molecular bowl of the {Cu(Tp(Ph))} moiety, which generates singlet oxygen as the reactive species in a type-II process.

  12. Sterically Demanding Oxidative Amidation of α‐Substituted Malononitriles with Amines Using O2

    PubMed Central

    Li, Jing

    2016-01-01

    Abstract An efficient amidation method between readily available 1,1‐dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α‐peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α‐carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles. PMID:27300467

  13. ω- versus (ω-1)-hydroxylation: Cytochrome P450 4B1 sterics make the call.

    PubMed

    Scott, Emily E

    2017-03-31

    Many family 4 cytochrome P450s play key roles in fatty acid hydroxylation at the terminal, or ω, carbon, but the mechanistic basis for this energetically disfavored regiostereochemistry has been less clear. A co-crystal structure of the rabbit family 4 enzyme CYP4B1 with its substrate octane reveals that the propensity for ω-hydroxylation is orchestrated by active-site sterics, partially mediated by an unusual heme-polypeptide ester bond. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Organizational barriers

    Treesearch

    Kenneth S. Blonski

    1995-01-01

    One of the traditional roles that prescribed fire has played in the fire management arena is reduction of hazardous fuel buildups under controlled, well-defined environmental conditions. However, our ability to use this tool effectively is blocked by many barriers. The preceding panel discussion about the causes of limited success in implementing prescribed burning...

  15. How do strain and steric interactions affect the reactions of aromatic compounds with free radicals? Characterization of the radicals formed by muonium addition to p-xylene and [2.2]paracyclophane by DFT calculations and muon spin spectroscopy.

    PubMed

    McKenzie, Iain; Scheuermann, Robert; Sedlak, Kamil

    2012-07-26

    Muoniated radicals were produced by the addition of muonium (Mu) to the aromatic compound p-xylene (1) in the solid and liquid states and to the strained aromatic compound [2.2]paracyclophane (2) in the solid state. The radicals were characterized by avoided level crossing muon spin resonance spectroscopy and identified by comparing the experimentally determined muon hyperfine coupling constants with values obtained from DFT calculations. Mu was observed to add to both the secondary and tertiary carbons of 1, with the relative yield of the Mu adduct of the tertiary carbons estimated to be ∼10% in the liquid phase. The relative yield of the tertiary adduct is much higher in the solid state although this cannot be calculated exactly due to the overlap of resonances and the apparent nonuniform distribution of the radical orientations. There are three possible addition sites in 2 due to the lower symmetry of the six-membered ring compared with 1. Mu can add to the secondary carbons either from the outside of 2, generating the "exo" adduct, or from the inside, generating the "endo" adduct. The relative yields of the exo, endo, and tertiary carbon adducts are 67.1(1), 21.8(1), and 11.1(1)%, respectively. The barriers to Mu addition at the different sites of isolated molecules were determined from DFT calculations. The barriers for Mu addition to 2 are lower than the barriers for Mu addition to 1, except for addition to the "endo" position, where the unfavorable steric interactions with the second ring of 2 raise the addition barrier considerably. The measured relative yields do not reflect the distribution of products calculated using the activation energies obtained from the DFT calculations due to strong steric interactions with neighboring molecules.

  16. Language barriers

    PubMed Central

    Ngwakongnwi, Emmanuel; Hemmelgarn, Brenda R.; Musto, Richard; King-Shier, Kathryn M.; Quan, Hude

    2012-01-01

    Abstract Objective To assess use of regular medical doctors (RMDs), as well as awareness and use of telephone health lines or telehealth services, by official language minorities (OLMs) in Canada. Design Analysis of data from the 2006 postcensal survey on the vitality of OLMs. Setting Canada. Participants In total, 7691 English speakers in Quebec and 12 376 French speakers outside Quebec, grouped into those who experienced language barriers and those with no language barriers. Main outcome measures Health services utilization (HSU) by the presence of language barriers; HSU measures included having an RMD, use of an RMD’s services, and awareness of and use of telephone health lines or telehealth services. Multivariable models examined the associations between HSU and language barriers. Results After adjusting for age and sex, English speakers residing in Quebec with limited proficiency in French were less likely to have RMDs (adjusted odds ratio [AOR] 0.66, 95% CI 0.50 to 0.87) and to use the services of their RMDs (AOR 0.65, 95% CI 0.50 to 0.86), but were more likely to be aware of the existence of (AOR 1.50, 95% CI 1.16 to 1.93) and to use (AOR 1.43, 95% CI 0.97 to 2.11) telephone health lines or telehealth services. This pattern of having and using RMDs and telehealth services was not observed for French speakers residing outside of Quebec. Conclusion Overall we found variation in HSU among the language barrier populations, with lower use observed in Quebec. Age older than 45 years, male sex, being married or in common-law relationships, and higher income were associated with having RMDs for OLMs. PMID:23242902

  17. Structural consequences of spin conversion in a sterically encumbered Ni(II) porphyrin

    SciTech Connect

    Barkigia, K.M.; Nelson, N.Y.; Renner, M.W.; Smith, K.M.; Fajer, J.

    1999-10-14

    The crystal structure of a pyridine-ligated, high-spin Ni(II) complex of 2,3,7,8,12,13,17,18-octabromo-5, 15-bis(isopropyl)-10,20-bis(isopropylidenyl) porphyrin, is reported and compared to the unligated, low-spin Ni(II) complex previously reported. The results demonstrate that conversion to high-spin Ni(II) in nonplanar, sterically encumbered porphyrins induces a significant core expansion about the Ni while nonplanarity is still retained. The expansion of the core parameters (Ni-N, Ct-C{alpha}, Ct-Cmexo) and the Ni-N{sub axial} distances are characteristic of the d{sub x{sup 2}{minus}y{sup 2}} orbital occupancies in high-spin Ni(II) porphyrins and document the structural consequences of the spin conversion in severely nonplanar Ni(II) porphyrins. The stereochemical results are particularly relevant to ligation effects in nonplanar Ni biomolecules and synthetic porphyrins increasingly used as biomimetic models of conformational effects in chromophores and prosthetic groups in vivo, and to the remarkably wide range of lifetimes observed for excited (d,d) states in nonplanar, sterically constrained Ni(II) porphyrins in which the d{sub x{sup 2}{minus}y{sup 2}} and d{sub z{sup 2}} orbitals are also populated.

  18. Conformational effects of peripheral substituents and axial ligands in sterically crowded porphyrins

    SciTech Connect

    Nurco, D.J.; Smith, K.M.; Fajer, J.

    1997-12-31

    Crystallographic results for peripherally substituted porphyrins illustrate effects of steric crowding, axial ligation and {pi}-{pi} interactions on the structures of metalloporphyrins that begin to resemble the architectures found for porphyrinic prosthetic groups and chromophores in vivo. (1) Metalloporphyrins with multiple peripheral substituents can adopt planar, saddled, ruffled or {open_quotes}wavy{close_quotes} conformations that persist upon axial ligation of the metal. (2) In porphyrins with substituents at all peripheral positions, the substituents form pockets that force the axial ligands to align in specific orientations relative to each other and to the axes defined by the porphyrin estrogens. (3) The enforced alignment of the axial ligands caused by the substituent pocket prevents aromatic ligands from rotating around the coordination axis with intriguing consequences: the axial ligands can be forced to tip off axis because of steric crowding by adjacent molecules in the crystal lattice. (4) In porphyrins with meso substituents only, the axial ligands are free to rotate but {pi}-{pi} interactions and collacial stacking between adjacent molecules in the crystal also induce off-axis ligand tilts.

  19. Role of water and steric constraints in the kinetics of cavity–ligand unbinding

    PubMed Central

    Tiwary, Pratyush; Mondal, Jagannath; Morrone, Joseph A.; Berne, B. J.

    2015-01-01

    A key factor influencing a drug’s efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity–ligand system using a metadynamics-based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, the unbinding time is found to be on the order of 4,000 s. In accordance with previous studies, we find that the cavity must pass through a region of sharp wetting transition manifested by sudden and high fluctuations in solvent density. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp wetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent MD studies at timescales previously unattainable, to our knowledge, obtaining direct and reliable pictures of the underlying physiochemical factors including free energies and rate constants. PMID:26371312

  20. Remote Steric Effect as a Facile Strategy for Improving the Efficiency of Exciplex-Based OLEDs.

    PubMed

    Hung, Wen-Yi; Wang, Ting-Chih; Chiang, Pin-Yi; Peng, Bo-Ji; Wong, Ken-Tsung

    2017-03-01

    This work reports a new strategy of introducing remote steric effect onto the electron donor for giving the better performance of the exciplex-based organic light-emitting device (OLED). The bulky triphenylsilyl group (SiPh3) was introduced onto the fluorene bridge of 4,4'-(9H-fluorene-9,9-diyl)bis(N,N-di-p-tolylaniline) (DTAF) to create remote steric interactions for increasing the possibility of effective contacts between electron-donating chromophores and acceptor molecules, rendering the resulting exciplex to have a higher photoluminescence quantum yield (PLQY). The green exciplex device based on DSDTAF:3N-T2T (1:1) as an emitting layer exhibits a low turn-on voltage of 2.0 V, high maximum efficiencies (13.2%, 42.9 cd A(-1), 45.5 lm W(-1)), which are higher than the device employed DTAF (without SiPh3 groups) (11.6%, 35.3 cd A(-1), 41.3 lm W(-1)) as donor under the same device structure. This strategy was further examined for blue exciplex, where the EQE was enhanced from 9.5% to 12.5% as the electron acceptor PO-T2T mixed with a tert-butyl group substituted carbazole-based donor (CPTBF) as the emitting exciplex in device. This strategy is simple and useful for developing high performance exciplex OLEDs.